Method for controlling particular insect pests by applying anthranilamide compounds

ABSTRACT

This invention pertains to a method for controlling lepidopteran, homopteran, hemipteran, thysanopteran and coleopteran insect pests comprising contacting the insects or their environment with an arthropodicidally effective amount of a compound of Formula I, its N-oxide or an agriculturally suitable salt thereof 
                         
wherein A and B and R 1  through R 8  are as defined in the disclosure.
 
     This invention further relates to a benzoxazinone compound of Formula 10 
                         
wherein R 4  through R 8  are as defined in the disclosure, useful for preparation of a compound of Formula I.

REFERENCE TO RELATED APPLICATIONS

This application is a continuation of application Ser. No. 12/717,982,filed Mar. 5, 2010, which is a divisional of application Ser. No.12/141,170, filed Jun. 18, 2008, now U.S. Pat. No. 7,696,233, which is acontinuation of application Ser. No. 10/483,115, filed on Jan. 7, 2004,which is a national filing under 35 U.S.C. 371 of InternationalApplication No. PCT/US02/25613, filed 13 Aug. 2002, which claimspriority benefit of Provisional Application 60/324,173, filed 21 Sep.2001 and Provisional Application 60/311,919, filed 13 Aug. 2001.

BACKGROUND OF THE INVENTION

This invention relates to a method of use for controlling invertebratepests in both agronomic and nonagronomic environments of certainanthranilamides, their N-oxides, agriculturally suitable salts andcompositions.

The control of invertebrate pests is extremely important in achievinghigh crop efficiency. Damage by invertebrate pests to growing and storedagronomic crops can cause significant reduction in productivity andthereby result in increased costs to the consumer. The control ofinvertebrate pests in forestry, greenhouse crops, ornamentals, nurserycrops, stored food and fiber products, livestock, household, and publicand animal health is also important. Many products are commerciallyavailable for these purposes, but the need continues for new compoundsthat are more effective, less costly, less toxic, environmentally saferor have different modes of action.

NL 9202078 discloses N-acyl anthranilic acid derivatives of Formula i asinsecticides

wherein, inter alia,

-   -   X is a direct bond;    -   Y is H or C₁-C₆ alkyl;    -   Z is NH₂, NH(C₁-C₃ alkyl) or N(C₁-C₃ alkyl)₂; and    -   R¹ through R⁹ are independently H, halogen, C₁-C₆ alkyl phenyl,        hydroxy, C₁-C₆ alkoxy or C₁-C₇ acyloxy.

SUMMARY OF THE INVENTION

This invention pertains to a method for controlling lepidopteran,homopteran, hemipteran, thysanopteran and coleopteran insect pestscomprising contacting the insects or their environment with anarthropodicidally effective amount of a compound of Formula I, itsN-oxide or an agriculturally suitable salt thereof

wherein

-   -   A and B are independently O or S;    -   R¹ is H, C₁-C₆ alkyl, C₂-C₆ alkoxycarbonyl or C₂-C₆        alkylcarbonyl;    -   R² is H or C₁-C₆ alkyl;    -   R³ is H; C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, or C₃-C₆        cycloalkyl, each optionally substituted with one or more        substituents selected from the group consisting of halogen, CN,        NO₂, hydroxy, C₁-C₄ alkyl, C₁-C₄ alkoxy, C₁-C₄ hydroalkoxy,        C₁-C₄ alkylthio, C₁-C₄ alkylsulfinyl, C₁-C₄ alkylsulfonyl, C₂-C₆        alkoxycarbonyl, C₂-C₆ alkylcarbonyl, C₃-C₆ trialkylsilyl,        phenyl, phenoxy, 5-membered heteroaromatic rings, and 6-membered        heteroaromatic rings; each phenyl, phenoxy, 5-membered        heteroaromatic ring, and 6-membered heteroaromatic ring        optionally substituted with one to three substituents        independently selected from the group consisting of C₁-C₄ alkyl,        C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₃-C₆ cycloalkyl, C₁-C₄ haloalkyl,        C₁-C₄ haloalkyenyl, C₂-C₄ haloalkynyl, C₃-C₆ halocycloalkyl,        halogen, CN, NO₂, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₁-C₄        alkylthio, C₁-C₄ alkylsulfinyl, C₁-C₄ alkylsulfonyl, C₁-C₄        alkylamino, C₂-C₈ dialkylamino, C₃-C₆ cycloalkylamino, C₄-C₈        (alkyl)(cycloalkyl)amino, C₂-C₄ alkylcarbonyl, C₂-C₆        alkoxycarbonyl, C₂-C₆ alkylaminocarbonyl, C₃-C₈        dialkylaminocarbonyl and C₃-C₆ trialkylsilyl, C₁-C₄ alkoxy;        C₁-C₄ alkylamino; C₂-C₈ dialkylamino; C₃-C₆ cycloalkylamino;        C₂-C₆ alkoxycarbonyl or C₂-C₆ alkylcarbonyl;    -   R⁴ is H, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₃-C₆ alkynyl, C₁-C₄        cycloalkyl, C₁-C₆ haloalkyl, CN, halogen, C₁-C₄ alkoxy, C₁-C₄        haloalkoxy or NO₂;    -   R⁵ is H, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₁-C₄ alkoxyalkyl, C₁-C₄        hydroxyalkyl, C(O)R¹⁰, CO₂R¹⁰, C(O)NR¹⁰R¹¹, halogen, C₁-C₄        alkoxy, C₁-C₄ haloalkoxy NR¹⁰R¹¹, N(R¹¹)C(O)R¹⁰, N(R¹¹)CO₂R¹⁰ or        S(O)_(n)R¹²;    -   R⁶ is H, C₁-C₆ alkyl, C₁-C₆ haloalkyl, halogen, CN, C₁-C₄ alkoxy        or C₁-C₄ haloalkoxy;    -   R⁷ is C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆        cycloalkyl, C₁-C₆ haloalkyl, C₂-C₆ haloalkenyl, C₂-C₆        haloalkynyl or C₃-C₆ halocycloalkyl; or    -   R⁷ is a phenyl ring, a benzyl ring, a 5- or 6-membered        heteroaromatic ring, a napthyl ring system or an aromatic 8-,        9-, or 10-membered fused heterobicyclic ring system, each ring        or ring system optionally substituted with one to three        substituents independently selected from R⁹;    -   R⁸ is H, C₁-C₆ alkyl, C₁-C₆ haloalkyl, halogen, C₁-C₄ alkoxy or        C₁-C₄ haloalkoxy;    -   each R⁹ is independently C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄        alkynyl, C₃-C₆ cycloalkyl, C₁-C₄ haloalkyl, C₂-C₄ haloalkenyl,        C₂-C₄ haloalkynyl, C₃-C₆ halocycloalkyl, halogen, CN, NO₂, C₁-C₄        alkoxy, C₁-C₄ haloalkoxy, C₁-C₄ alkylthio, C₁-C₄ alkylsulfinyl,        C₁-C₄ alkylsulfonyl, C₁-C₄ alkylamino, C₂-C₈ dialkylamino, C₃-C₆        cycloalkylamino, C₄-C₈ (alkyl)(cycloalkyl)amino, C₂-C₄        alkylcarbonyl, C₂-C₆ alkoxycarbonyl, C₂-C₆ alkylaminocarbonyl,        C₃-C₈ dialkylaminocarbonyl or C₃-C₆ trialkylsilyl;    -   R¹⁰ is H, C₁-C₄ alkyl or C₁-C₄ haloalkyl;    -   R¹¹ is H or C₁-C₄ alkyl;    -   R¹² is C₁-C₄ alkyl or C₁-C₄ haloalkyl; and    -   n is 0, 1 or 2.

This invention also relates to such a method wherein an invertebratepest or its environment is contacted with a composition comprising abiologically effective amount of a compound of Formula I or acomposition comprising a compound of Formula I and a biologicallyeffective amount of a at least one additional biologically activecompound.

This invention further relates to a benzoxazinone compound of Formula 10

wherein

-   -   R⁴, R⁵, R⁶, R⁷ and R⁸ are defined as above in Formula I.

The compound of Formula 10 is useful as a synthetic intermediate forpreparing a compound of Formula I.

DETAILS OF THE INVENTION

In the above recitations, the term “alkyl”, used either alone or incompound words such as “alkylthio” or “haloalkyl” includesstraight-chain or branched alkyl, such as, methyl, ethyl, n-propyl,i-propyl, or the different butyl, pentyl or hexyl isomers. “Alkenyl”includes straight-chain or branched alkenes such as 1-propenyl,2-propenyl, and the different butenyl, pentenyl and hexenyl isomers.“Alkenyl” includes straight-chain or branched alkynes such as1-propynyl, 2-propynyl and the different butynyl, pentynyl and hexynylisomers. “Alkynyl” an also include moieties comprised of multiple triplebonds such as 2,5-hexadiynyl. “Alkoxy” includes, for example, methoxy,ethoxy, n-propyloxy, isopropyloxy and the different butoxy, pentoxy andhexyloxy isomers. “Alkoxyalkyl” denotes alkoxy substitution on alkyl.Examples of “alkoxyalkyl” include CH₃OCH₂, CH₃OCH₂CH₂, CH₃CH₂OCH₂,CH₃CH₂CH₂CH₂OCH₂ and CH₃CH₂OCH₂CH₂. “Alkylthio” includes branched orstraight-chain alkylthio moieties such as methylthio, ethylthio, and thedifferent propylthio, butylthio, penthylthio and hexylthio isomers.“Cycloalkyl” includes, for example, cyclopropyl, cyclobutyl, cyclopentyland cyclohexyl.

The term “heterocyclic ring” or heterocyclic ring system” denotes ringsor ring systems in which at least one ring atom is not carbon andcomprises 1 to 4 heteroatoms independently selected from the groupconsisting of nitrogen, oxygen and sulfur, provided that eachheterocyclic ring contains no more than 4 nitrogens, no more than 2oxygens and no more than 2 sulfurs. The heterocyclic ring can beattached through any available carbon or nitrogen by replacement ofhydrogen on said carbon or nitrogen. The term “aromatic ring system”denotes fully unsaturated carbocycles and heterocycles in which at leastone ring of the polycyclic ring system is aromatic (where aromaticindicates that the Hückel rule is satisfied for the ring system). Theterm “heteroaromatic ring” denotes fully aromatic rings in which atleast one ring atom is not carbon and comprises 1 to 4 heteroatomsindependently selected from the group consisting of nitrogen, oxygen andsulfur, provided that each heterocyclic ring contains no more than 4nitrogens, no more than 2 oxygens and no more than 2 sulfurs (wherearomatic indicates that the Hückel rule is satisfied). The heterocyclicring can be attached through any available carbon or nitrogen byreplacement of hydrogen on said carbon or nitrogen. The term “aromaticheterocyclic ring system” includes fully aromatic heterocycles andheterocycles in which at least one ring of a polycyclic ring system isaromatic (where aromatic indicates that the Hückel rule is satisfied).The term “fused heterocyclic ring system” includes a ring systemcomprised of two fused rings in which at least one ring atom is notcarbon and can be aromatic or non aromatic, as defined above.

The term “halogen”, either alone or in compound words such as“haloalkyl”, includes fluorine, chlorine, bromine or iodine. Further,when used in compound words such as “haloalkyl”, said alkyl may bepartially or fully substituted with halogen atoms which may be the sameor different. Examples of “haloalkyl” include F₃C, ClCH₂, CF₃CH₂ andCF₃CCl₂. The terms “haloalkenyl”, “haloalkynyl”, “haloalkoxy”, and thelike, are defined analogously to the term “haloalkyl”. Examples of“haloalkenyl” include (Cl)₂C═CHCH₂ and CF₃CH₂CH═CHCH₂. Examples of“haloalkynyl” include HC≡CCHCl, CF₃C≡C, CCl₃C≡C and FCH₂C≡CCH₂. Examplesof “haloalkoxy” include CF₃O, CCl₃CH₂O, HCF₂CH₂CH₂O and CF₃CH₂O.

The total number of carbon atoms in a substituent group is indicated bythe “C_(i)-C_(j)” prefix where j and j are numbers from 1 to 8. Forexample, C₁-C₄ alkylsulfonyl designates methylsulfonyl throughbutylsulfonyl; C₂ alkoxyalkyl designates CH₃OCH₂; C₃ alkoxyalkyldesignates, for example, CH₃CH(OCH₃), CH₃OCH₂CH₂ or CH₃CH₂OCH₂; and C₄alkoxyalkyl designates the various isomers of an alkyl group substitutedwith an alkoxy group containing a total of four carbon atoms, examplesincluding CH₃CH₂CH₂OCH₂ and CH₃Ch₂OCH₂CH₂. In the above recitations,when a compound of Formula I comprises a heterocyclic ring, allsubstituents are attached to this ring through any available carbon ornitrogen by replacement of a hydrogen on said carbon or nitrogen.

The term “optionally substituted with one to three substituents”indicates that one to three of the available positions on the group maybe substituted. When a group contains a substituent which can behydrogen, for example R⁶, then, when this substituent is taken ashydrogen, it is recognized that this is equivalent to said group beingunsubstituted.

Compounds of Formula I can exist as one or more stereoisomers. Thevarious stereoisomers include enantiomers, diastereomers, attopisomersand geometric isomers. One skilled in the art will appreciate that onestereoisomer may be more active and/or may exhibit beneficial effectswhen enriched relative to the other stereoisomer(s) or when separatedfrom the other stereoisomer(s). Additionally, the skilled artisan knowshow to separate, enrich, and/or to selectively prepare saidstereoisomers. Accordingly, the compounds of Formula I may be present asa mixture of stereoisomers, individual stereoisomers, or as an opticallyactive form. Similarly, compounds of Formula 10 can exist as one or morestereoisomers. The various stereoisomers include enantiomers,diastereomers, atropisomers and geometric isomers. One skilled in theart will appreciate that one stereoisomer of a compound of Formula 10may be more useful in preparing a specific stereoisomer of Formula I.Additionally, the skilled artisan knows how to separate, enrich, and/orto selectively prepare said stereoisomers. Accordingly, the compounds ofFormula 10 may be present as a mixture of stereoisomers, individualstereoisomers, or as an optically active form.

The salts of the compounds of Formula I include acid-addition salts withinorganic or organic acids such as hydrobromic, hydrochloric, nitric,phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic,oxalic, propionic, salicyclic, tartaric, 4-toluenesulfonic or valericacids.

As noted above, R⁷ is (among others) a phenyl, a benzyl, a 5- or6-membered heteroaromatic ring, a naphthyl ring system or an aromatic8-, 9- or 10-membered fused heterobicyclic ring system, each ring orring system optionally substituted with one to three substituentsindependently selected from R⁹. The term “optionally substituted” inconnection with these R⁷ groups refers to groups which are unsubstitutedor have at least one non-hydrogen substituent that does not extinguishthe invertebrate pest control activity possessed by the unsubstitutedanalog. Note also that J-1 through J-4 below denote 5- or 6-memberedheteroaromatic rings. An example of a phenyl ring optionally substitutedwith 1 to 3 R⁹ is the ring illustrated as J-5 in Exhibit 1, wherein r isan integer from 0 to 3. An example of a benzyl ring optionallysubstituted with 1 to 3 R⁹ is the ring illustrated as J-6 in Exhibit 1,wherein r is an integer from 0 to 3. An example of naphthyl ring systemoptionally substituted with 1 to 3 R⁹ is illustrated in J-59 in Exhibit1, wherein r is an integer from 0 to 3. Examples of a 5- or 6-memberedheteroaromatic ring optionally substituted with 1 to 3 R⁹ include therings J-7 through J-58 illustrated in Exhibit 1 wherein r is an integerfrom 0 to 3. Note that J-7 through J-26 are examples of J-1, J-27through J-41 are examples of J-2, and J-45 through J-58 are examples ofJ-3 and J-4. The nitrogen atoms that require substitution to fill theirvalence are substituted with H or R⁹. Note that some J groups can onlybe substituted with less than 3 R⁹ groups (e.g. J-19, J-20, J-23 throughJ-26 and J-37 through J-40 can only be substituted with one R⁹). Exampleof aromatic 8-, 9- or 10-membered fuse heterobicyclic ring systemsoptionally substituted with 1 to 3 R⁹ include J-60 through J-90illustrated in Exhibit 1 wherein r is an integer from 0 to 3. AlthoughR⁹ groups are shown in the structures J-5 through J-90, it is noted thatthey do not need to be present since they are optional substituents.Note that when the attachment point between (R⁹)_(r) and the J group isillustrated as floating, (R⁹)_(r) can be attached to any availablecarbon atom of the J group. Note that when the attachment point on the Jgroup is illustrated as floating, the J group can be attached to theremainder of Formula I through any available carbon of the J group byreplacement of a hydrogen atom.

Preferred methods for reasons of cost, ease of synthesis or application,and/or biological efficacy are:

Preferred 1. Methods comprising a compound of Formula I wherein

-   -   A and B are both O;    -   R⁷ is a phenyl ring or a 5- or 6-membered heteroaromatic ring        selected from the group consisting of

-   -   -   each ring optionally substituted with one to three            substituents independently selected from R⁹;

    -   Q is O, S, NH or NR⁹; and

    -   W, X, Y and Z are independently N, CH or CR⁹, provided that in        J-3 and J-4 at least one of W, X, Y or Z is N.

Preferred 2. Methods of Preferred 1 wherein

-   -   R¹, R² and R⁸ are all H;    -   R³ is C₁-C₄ alkyl optionally substituted with halogen, CN, OCH₃        or S(O)_(p)CH₃;    -   R⁴ is CH₃, CF₃, OCF₃, OCHF₂, CN or halogen;    -   R⁵ is H, CH₃ or halogen;    -   R⁶ is CH₃, CF₃ or halogen;    -   R⁷ is phenyl or 2-pyridinyl, each optionally substituted; and    -   p is 0, 1 or 2.

Preferred 3. Methods of Preferred 2 wherein R³ is C₁-C₄ alkyl and R⁶ isCF₃.

Preferred 4. A compound of Preferred 2 wherein R³ is C₁-C₄ alkyl and R⁶is Cl or Br.

Preferred compounds of Formula 10 are:

Preferred A. Compounds of Formula 10 wherein

-   -   R⁷ is a phenyl ring or a 5- or 6-membered heteroaromatic ring        selected from the group consisting of

-   -   -   each ring optionally substituted with one to three            substituents independently selected from R⁹;

    -   Q is O, S, NH or NR⁹; and

    -   W, X, Y and Z are independently N, CH or CR⁹, provided that in        J-3 and J-4 at least one of W, X, Y and Z is N.

Preferred B. Compounds of Preferred A wherein

-   -   R⁸ is H;    -   R⁴ is CH₃, CF₃, OCF₃, OCHF₂, CN or halogen;    -   R⁵ is H, CH₃ or halogen;    -   R⁶ is CH₃, CF₃ or halogen;    -   R⁷ is phenyl or 2-pyridinyl, each optionally substituted.

Preferred C. Compounds of Preferred B wherein R⁶ is CF₃.

Preferred D. Compounds of Preferred B wherein R⁶ is Cl or Br.

Of note are compounds of Formula 10 wherein R⁴ is at the 2 position andis CH₃, Cl or Br; R⁵ is at the 4 position and is F, Cl, Br, I or CF₃; R⁶is CF₃, Cl or Br; R⁷ is 3-Cl-2-pyridinyl or 3-Br-2-pyridinyl; and R⁸ isH.

One or more of the following methods and variations as described inSchemes 1-22 can be used to prepare the compounds of Formula I. Thedefinitions of A, B and R¹ through R⁹ in the compounds of Formulae 2-40below are as defined above in the Summary of the Invention unlessindicated otherwise. Compounds of Formulae Ia-d, 2a-d, 3a, 4a-d, 5a-b,17a-c, 18a and 32a-b are various subsets of the compounds of Formula I,2, 3, 4, 5, 17, 18 and 32. In the schemes, Het is the moiety shownbelow:

A typical method for preparation of a compound of Formula Ia isdescribed in Scheme 1.

The method of Scheme 1 involves coupling of an amine of Formula 2 withan acid chloride of Formula 3 in the presence of an acid scavenger toprovide the compound of Formula Ia. Typical acid scavengers includeamine bases such as triethylamine, N,N-diisopropylethylamine andpyridine; other scavengers include hydroxides such as sodium andpotassium hydroxide and carbonates such as sodium carbonate andpotassium carbonate. In certain instances it is useful to usepolymer-supported acid scavengers such as polymer-boundN,N-diisopropylethylamine and polymer-bound 4-(dimethylamino)pyridine.The coupling can be run in a suitable inert solvent such astetrahydrofuran, dioxane, diethylether or dichloromethane to afford theanilide of Formula Ia.

A thioamide of Formula Ib can be obtained in a subsequent step from thecorresponding amide of Formula Ia by treatment with one of a variety ofstandard thio transfer reagents including phosphorus pentasulfide andLawesson's reagent(2,4-bis(4-methoxyphenyl-1,3-dithia-2,4-diphosphentane-2,4-disulfide).

As shown in Scheme 2, an alternate procedure for the preparation ofcompounds of Formula Ia involves coupling of an amine of Formula 2 withan acid of Formula 4 in the presence of a dehydrating agent such asdicyclohexylcarbodiimide (DCC), 1,1′-carbonyl-diimidazole,bis(2-oxo-3-oxazolidinyl)phosphinic chloride orbenzotriazol-1-yloxy-tris-(dimethylamino)phosphoniumhexafluorophosphate.

Polymer-supported reagents are again useful here, such as polymer-boundcyclohexylcarbodiimide. The coupling can be run in a suitable inertsolvent such as dichloromethane or N,N-dimethylformamide. The syntheticmethods of Schemes 1 and 2 are just representative examples of a widevariety of coupling methods useful for the preparation of Formula Icompounds; the synthetic literature is extensive for this type ofcoupling reaction.

One skilled in the art will also realize that add chlorides of Formula 3may be prepared from acids of Formula 4 by numerous well-known methods.For example, acid chlorides of Formula 3 are readily made fromcarboxylic acids of Formula 4 by reacting the carboxylic acid 4 withthionyl chloride or oxalyl chloride in an inert solvent such as tolueneor dichloromethane in the presence of a catalytic amount ofN,N-dimethylformamide.

As shown in Scheme 3, amines of Formula 2a are typically available fromthe corresponding 2-nitrobenzamides of Formula 5 via catalytichydrogenation of the nitro group.

Typical procedures involve reduction with hydrogen in the presence of ametal catalyst such as palladium on carbon or platinum oxide and inhydroxylic solvents such as ethanol and isopropanol. Amines of Formula2a can also be prepared by reduction with zinc in acetic acid. Theseprocedures are well documented in the chemical literature. R¹substituents such as C₁-C₆ alkyl can be introduced at this stage throughwell known methodologies including either direct alkylation or throughthe generally preferred method of reductive alkylation of the amine. Asis further shown in Scheme 3, a commonly employed procedure is tocombine the amine 2a with an aldehyde in the presence of a reducingagent such as sodium cyanoborohydride to produce the Formula 2bcompounds where R¹ is C₁-C₆ alkyl.

Scheme 4 shows that compounds of Formula Ic can be alkylated or acylatedwith a suitable alkylating or acylating agent such as an alkyl halide,alkyl chloroformate or acyl chloride in the presence of a base such assodium hydride or n-butyllithium in an inert solvent such astetrahydrofuran or N,N-dimethylformamide to afford anilides of FormulaId wherein R¹ is other than hydrogen.

The intermediate amides of Formula 5a are readily prepared fromcommercially available 2-nitrobenzoic acids. Typical methods for amideformation can be used. As shown in Scheme 5, these methods includedirect dehydrative coupling of acids of Formula 6 with amines of Formula7 using for example DCC, and conversion of the acids to activated formssuch as the acid chlorides or anhydrides and subsequent coupling withamines to form amides of Formula 5a.

Alkyl chloroformates, such as ethyl chloroformate or isopropylchloroformate, are especially useful reagents for this type of reactioninvolving activation of the acid. The chemical literature is extensiveregarding methods for amide formation. Amides of Formula 5a are readilyconverted to thioamides of Formula 5b by using commercially availablethio transfer reagents such as phosphorus pentasulfide and Lawesson'sreagent.

Intermediate anthranilic amides of Formula 2c or 2d may also be preparedfrom isatoic anhydrides of Formula 8 or 9, respectively, as shown inScheme 6.

Typical procedures involve combination of equimolar amounts of the amine7 with the isatoic anhydride in polar aprotic solvents such as pyridineand N,N-dimethylformamide at temperatures ranging from room temperatureto 100° C. R¹ substituents such as alkyl and substituted alkyl may beintroduced by the base-catalysed alkylation of isatoic anhydride 8 withknown alkylating reagents R¹-Lg (wherein Lg is a nucleophilicdisplaceable leaving group such as halides alkyl ox aryl sulfonates oralkyl sulfates) to provide the alkyl substituted intermediate 9. Isatoicanhydrides of Formula 8 may be made by methods described in Coppola,Synthesis 1980, 505-36.

As shown in Scheme 7, an alternate procedure for the preparation ofspecific compounds of Formula Ic involves reaction of an amine 7 with abenzoxazinone of Formula 10.

The reaction of Scheme 7 can be run neat or in a variety of suitablesolvents including tetrahydrofuran, diethyl ether, pyridine,dichloromethane or chloroform with optimum temperatures ranging fromroom temperature to the reflux temperature of the solvent. The generalreaction of benzoxazinones with amines to produce anthranilamides iswell documented in the chemical literature. For a review ofbenzoxazinone chemistry see Jakobsen et al., Biorganic and MedicinalChemistry 2880, 8, 2095-2103 and references cited therein. See alsoCoppola, J. Heterocyclic Chemistry 1999, 36, 563-588.

Benzoxazinones of Formula 10 can be prepared by a variety of procedures.Two procedures that are especially useful are detailed in Schemes 8-9.In Scheme 8, a benzoxazinone of Formula 10 is prepared directly viacoupling of a pyrazolecarboxylic acid of Formula 4a with an anthranilicacid of Formula 11.

This involves sequential addition of methanesulfonyl chloride in thepresence of a tertiary amine such as triethylamine or pyridine to apyrazolecarboxylic acid of Formula 4a, followed by the addition of ananthranilic acid of Formula 11, followed by a second addition oftertiary amine and methanesulfonyl chloride. This procedure generallyaffords good yields of the benzoxazinone and is illustrated with greaterdetail in Examples 6 and 8.

Scheme 9 depicts an alternate preparation for benzoxazinones of Formula10 involving coupling of a pyrazole acid chloride of Formula 3a with anisatoic anhydride of Formula 8 to provide the Formula 10 benzoxazinonedirectly.

Solvents such as pyridine or pyridine/acetonitrile are suitable for thisreaction. The acid chlorides of Formula 3a are available from thecorresponding acids of Formula 4a by a variety of synthetic methods suchas chlorination with thionyl chloride or oxalyl chloride.

Isatoic anhydrides of Formula 8 can be prepared from isatins of Formula13 as outlined in Scheme 10.

Isatins of Formula 13 are obtained from aniline derivatives of Formula12 using methods known in the literature. Oxidation of isatin 13 withhydrogen peroxide generally affords good yields in the correspondingisatoic anhydride 8 (Angew. Chem. Int. Ed. Engl. 1980, 19, 222-223).Isatoic anhydrides are also available from the anthranilic acids 11 viamany known procedures involving reaction of 11 with phosgene or aphosgene equivalent.

The syntheses of representative acids of Formula 4 are depicted inSchemes 11-16. Syntheses of pyrazoles of Formula 4a are shown in Scheme11.

The synthesis of compounds of Formula 4a is Scheme 11 involves as thekey step introduction of the R⁷ substituent via alkylation of arylationof the pyrazole of Formula 14 with compounds of Formula 15 (wherein Lgis a leaving group as defined above). Oxidation of the methyl groupaffords the pyrazole carboxylic acid. Some of the more preferred R⁶groups include haloalkyl.

Synthesis of pyrazoles of Formula 4a is also shown in Scheme 12.

These acids may be prepared via metallation and carboxylation ofcompounds of Formula 18 as the key step. The R⁷ group is introduced in amanner similar to that of Scheme 11, i.e. via alkylation or arylationwith a compound of Formula 15. Representative R⁶ groups include e.g.cyano, haloalkyl and halogen.

This procedure is particularly useful for preparing1-(2-pyradinyl)pyrazolecarboxylic acids of Formula 4b as shown in Scheme13.

Reaction of a pyrazole of Formula 11 with a 2,3-dihalopyridine ofFormula 15a affords good yields of the 1-pyridylpyrazole of Formula 18awith good specificity for the desired regiochemistry. Metallation of 18awith lithium diisopropylamide (LDA) followed by quenching of the lithiumsalt with carbon dioxide affords the 1-(2-pyridinyl)pyrazolecarboxylicacid of Formula 4b. Additional details for these procedures are providedin Examples 1, 3, 6, 8 and 10.

The synthesis of pyrroles of Formula 4c is described in Scheme 14.

Scheme 14 involves reaction of an optionally substituted phenylhydrazine of Formula 19 with a ketopyruvate of Formula 20 to yieldpyrazole esters of Formula 21. Hydrolysis of the esters affords thepyrazole acids of Formula 4c. This procedure is particularly useful forthe preparation of compounds in which is optionally substituted phenyland R⁶ is haloalkyl.

An alternate synthesis of pyrazole acids of Formula 4c is described inScheme 15.

The method of Scheme 15 involves 3+2 cycloaddition of an appropriatelysubstituted iminohalide 22 with either substituted propiolates ofFormula 23 or acrylates of Formula 25. Cycloaddition with an acrylaterequires additional oxidation of the intermediate pyrazoline to thepyrazole. Hydrolysis of the esters affords the pyrazole acids of Formula4c. Preferred iminohalides for this reaction include the trifluoromethyliminochloride of Formula 26 and the iminodibromide of Formula 27.Compounds such as 26 are known (J. Heterocycl. Chem. 1985, 22(2),565-8), Compounds such as 27 are available by known methods (TetrahedronLetters 1999, 40, 2605). These procedures are particularly useful forthe preparation of compounds where R⁷ is optionally substituted phenyland R⁶ is haloalkyl or bromo.

The starting pyrazoles of Formula 17 are known compounds or can beprepared according to known methods. The pyrazole of Formula 17a (thecompound of Formula 17 wherein R⁶ is CF₃ and R⁸ is H) can be prepared byliterature procedures (J. Fluorine Chem. 1991, 53(1), 61-70). Thepyrazoles of Formula 17c (compounds of Formula 17 wherein R⁶ is Cl or Brand R⁸ is H) can also be prepared by literature procedures (Chem. Ber.1996, 99(10), 3350-7). A useful alternative method for the preparationof compound 17c is depicted b Scheme 16.

In the method of Scheme 16, metallation of the sulfamoyl pyrazole ofFormula 28 with n-butyllithium followed by direct halogenation of theanion with either hexachloroethane (for R⁶ being Cl) or1,2-dibromotetrachloroethane (for R⁶ being Br) affords the halogenatedderivatives of Formula 29. Removal of the sulfamoyl group withtrifluoroacetic acid (TFA) at room temperature proceeds cleanly and ingood yield to afford the pyrazoles of Formula 17c. One skilled in theart will recognize that Formula 17c is a tautomer of Formula 17b.Further experimental details for these procedures are described inExamples 8 and 10.

Pyrazolecarboxylic acids of Formula 4d wherein R⁶ is H, C₁-C₆ alkyl orC₁-C₆ haloalkyl can be prepared by the method outlined in Scheme 17.

Reaction of a compound of Formula 30 wherein R¹³ is C₁-C₄ alkyl with asuitable base in a suitable organic solvent affords the cyclized productof Formula 31 after neutralization with an acid such as acetic acid. Thesuitable base can be, for example but not limitation, sodium hydride,potassium t-butoxide, dimsyl sodium (CH₃S(O)CH₂ ⁻Na⁺) alkali metal (suchas lithium, sodium or potassium) carbonates or hydroxides, tetraalkyl(such as methyl, ethyl or butyl)ammonium fluorides or hydroxides, or2-tert-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphonine.The suitable organic solvent can be, for example but not limitation,acetone, acetonitrile, tetrahydrofuran, dichloromethane,dimethylsulfoxide, or N,N-dimethylformamide. The cyclization reaction isusually conducted in a temperature range from about 0 to 120° C. Theeffects of solvent, base, temperature and addition time are allinterdependent, and choice of reaction conditions is important tominimize the formation of byproducts. A preferred base istetrabutylammonium fluoride.

Dehydration of the compound of Formula 31 to give the compound ofFormula 32, followed by converting the carboxylic ester function tocarboxylic acid, affords the compound of Formula 4d. The dehydration iseffected by treatment with a catalytic amount of a suitable acid. Thiscatalytic acid can be, for example but not limitation, sulfuric acid.The reaction is generally conducted using an organic solvent. As oneskilled in the art will realize, dehydration reactions may be conductedin a wide variety of solvents in a temperature range generally betweenabout 0 and 200° C., more preferably between about 0 and 100° C. For thedehydration in the method of Scheme 17, a solvent comprising acetic acidand temperatures of about 65° C. are preferred. Carboxylic estercompounds can be converted to carboxylic acid compounds by numerousmethods including nucleophilic cleavage under anhydrous conditions orhydrolytic methods involving the use of either acids or bases (see T. W.Greene and P. G. M. Wuts. Protective Groups in Organic Synthesis, 2nded., John Wiley & Sons, Inc., New York, 1991, pp. 224-269 for a reviewof methods). For the method of Scheme 17, base-catalyzed hydrolyticmethods are preferred. Suitable bases include alkali metal (such aslithium, sodium or potassium) hydroxides. For example, the ester can bedissolved in a mixture of water and an alcohol such in ethanol. Upontreatment with sodium hydroxide or potassium hydroxide, the ester issaponified to provide the sodium or potassium salt of the carboxylicacid. Acidification with a strong acid, such as hydrochloric acid orsulfuric acid, yields the carboxylic acid of Formula 4d. The carboxylicacid can be isolated by methods known to those skilled in the art,including crystallization, extraction and distillation.

Compounds of Formula 30 can be prepared by the method outlined in Scheme18.

wherein R⁶ is H, C₁-C₆ alkyl or C₁-C₆ haloalkyl and R¹³ is C₁-C₄ alkyl.

Treatment of a hydrazine compound of Formula 33 with a ketone of Formula34 in a solvent such as water, methanol or acetic acid gives thehydrazone of Formula 35. One skilled in the art will recognize that thisreaction may require catalysis by an optional acid and may also requireelevated temperatures depending on the molecular substitution pattern ofthe hydrazone of Formula 35. Reaction of the hydrazone of Formula 35with the compound of Formula 36 in a suitable organic solvent such as,for example but not limitation, dichloromethane or tetrahydrofuran inthe presence of an acid scavenger such as triethylamine provides thecompound of Formula 30. The reaction is usually conducted at atemperature between about 0 and 100° C. Further experimental details forthe method of Scheme 18 are illustrated in Example 17. Hydrazinecompounds of Formula 33 can be prepared by standard methods, such as bycontacting the corresponding halo compound of Formula 15a withhydrazine.

Pyrazolecarboxylic acids of Formula 4d wherein R⁶ in halogen can beprepared by the method outlined in Scheme 19.

wherein R¹³ is C₁-C₄ alkyl.

Oxidization of the compound of Formula 37 optionally in the presence ofacid to give the compound of Formula 32 followed by conversion of thecarboxylic ester function to the carboxylic acid provides the compoundof Formula 4d. The oxidizing agent can be hydrogen peroxide, organicperoxides, potassium, persulfate, sodium persulfate, ammoniumpersulfate, potassium monopersulfate (e.g., Oxone®) or potassiumpermanganate. To obtain complete conversion, at least one equivalent ofoxidizing agent versus the compound of Formula 37 should be used,preferably between about one to two equivalents. This oxidation istypically carried out in the presence of a solvent. The solvent can bean ether, such as tetrahydrofuran, p-dioxane and the like, an organicester, such as ethyl acetate, dimethyl carbonate and the like, or apolar aprotic organic such as N,N-dimethylformamide, acetonitrile andthe like. Acids suitable for use in the oxidation step include inorganicacids, such as sulfuric acid, phosphoric acid and the like, and organicacids, such as acetic acid, benzoic acid and the like. The acid, whenused, should be used in greater than 0.1 equivalents versus the compoundof Formula 37. To obtain complete conversion, one to five equivalents ofacid can be used. The preferred oxidant is potassium persulfate and theoxidation is preferably carried out in the presence of sulfuric acid.The reaction can be carried out by mixing the compound of Formula 37 inthe desired solvent and, if used, the acid. The oxidant can then beadded at a convenient rate. The reaction temperature is typically variedfrom as low as about 0° C. up to the boiling point of the solvent inorder to obtain a reasonable reaction time to complete the reaction,preferably less than 8 hours. The desired product, a compound of Formula32 can be isolated by methods known to those skilled in the art,including crystallization, extraction and distillation. Methods suitablefor converting the ester of Formula 32 to the carboxylic acid of Formula4d are already described for Scheme 17. Further experimental details forthe method of Scheme 19 are illustrated in Examples 12 and 13.

Compounds of Formula 37 can be prepared from corresponding compounds ofFormula 38 as shown in Scheme 20.

wherein R¹³ is C₁-C₄ alkyl and R⁶ is halogen.

Treatment of a compound of Formula 38 with a halogenating reagent,usually in the presence of a solvent, affords the corresponding halocompound of Formula 37. Halogenating reagents that can be used includephosphorus oxyhalides, phosphorus trihalides, phosphorus pentahalides,thionyl chloride, dihalotrialkylphosphoranes,dihalodiphenylphosphoranes, oxalyl chloride and phosgene. Preferred arephosphorus oxyhalides and phosphorus pentahalides. To obtain completeconversion, at least 0.33 equivalents of phosphorus oxyhalide versus thecompound of Formula 38 (i.e., the mole ratio of phosphorus oxyhalide toFormula 18 is at least 0.33) should be used, preferably between about0.33 and 1.2 equivalents. To obtain complete conversion, at least 0.20equivalents of phosphorus pentahalide versus the compound of Formula 38should be used, preferably between about 0.20 and 1.0 equivalents.Compounds of Formula 38 wherein R¹³ is C₁-C₄ alkyl are preferred forthis reaction. Typical solvents for this halogenation includehalogenated alkanes, such as dichloromethane, chloroform, chlorobutaneand the like, aromatic solvents, such a benzane, xylene, chlorobenzeneand the like, ethers, suck as tetrahydrofuran, p-dioxane, diethyl ether,and the like, and polar aprotic solvents such as acetonitrile,N,N-dimethylformamide and the like. Optionally, an organic base, such astriethylamine, pyridine, N,N-dimethylaniline or the like can be added.Addition of a catalyst, such as N,N-dimethylformamide, is also anoption. Preferred in the process in which the solvent is acetonitrileand a base is absent. Typically, neither a base nor a catalyst isrequired when acetonitrile solvent is used. The preferred process isconducted by mixing the compound of Formula 38 in acetonitrile. Thehalogenating reagent is then added over a convenient time, and themixture is then held at the desired temperature until the reaction iscomplete. The reaction temperature is typically between 20° C. and theboiling point of acetonitrile, and the reaction time is typically lessthan 2 hours. The reaction mass is then neutralized with an inorganicbase, such as sodium bicarbonate, sodium hydroxide and the like, or anorganic base, such as sodium acetate. The desired product, a compound ofFormula 37, can be isolated by methods known to those skilled in theart, including crystallization, extraction and distillation.

Alternatively, compounds of Formula 37 wherein R⁶ is halogen can beprepared by treating the corresponding compounds of Formula 37 whereinR⁶ is a different halogen (e.g., Cl for making Formula 37 wherein R³ isBr) or a sulfonate group such as p-toluenesulfonate, benzenesulfonateand methanesulfonate with the appropriate hydrogen halide. By thismethod the R⁶ halogen or sulfonate substituent on the Formula 37starting compound is replaced with, for example, Br or Cl from hydrogenbromide or hydrogen chloride, respectively. The reaction is conducted ina suitable solvent such as dibromomethane, dichloromethane oracetonitrile. The reaction can be conducted at or near atmosphericpressure or above atmospheric pressure in a pressure vessel. When R⁶ inthe starting compound of Formula 37 is a halogen, such as Cl, thereaction is preferably conducted in such a way that the hydrogen halidegenerated from the reaction is removed by sparging or other suitablemeans. The reaction can be conducted between about 0 and 100° C., mostconveniently near ambient temperature (e.g., about 10 to 40° C.), andmore preferably between about 20 and 30° C. Addition of a Lewis acidcatalyst (such as aluminum tribromide for preparing Formula 37 whereinR⁶ is Br) can facilitate the reaction. The product of Formula 37 isisolated by the usual methods known to those skilled in the art,including extraction, distillation and crystallization. Further detailsfor this process are illustrated in Example 14.

Starting compounds of Formula 37 wherein R⁶ is Cl or Br can be preparedfrom corresponding compounds of Formula 38 as already described.Starting compounds of Formula 37 wherein R⁶ is a sulfonate group canlikewise be prepared from corresponding compounds of Formula 38 bystandard methods such as treatment with a sulfonyl chloride (e.g.,p-toluenesulfonyl chloride) and base such as a tertiary amine (e.g.,triethylamine) in a suitable solvent such as dichloromethane; furtherdetails for this process are illustrated in Example 15.

Pyrazolecarboxylic acids of Formula 4d wherein R⁶ is C₁-C₄ alkoxy orC₁-C₄ haloalkoxy can also be prepared by the method outlined in Scheme21.

wherein R¹³ is C₁-C₄ alkyl, and X is a leaving group.

In this method, instead of being halogenated as shown in Scheme 20, thecompound of Formula 38 is oxidized to the compound of Formula 32a. Thereaction conditions for this oxidation are as already described for theconversion of the compound of Formula 37 to the compound of Formula 32in Scheme 19.

The compound of Formula 32a is then alkylated to form the compound ofFormula 32b by contact with an alkylating agent CF₃CH₂X (39) in thepresence of a base. In the alkylating agent 39, X is a nucleophilicreaction leaving group such as halogen (e.g., Br, I), OS(O)₂CH₃(methanesulfonate), OS(O)₂CF₃, OS(O)₂Ph-p-CH₃ (p-toluenesulfonate), andthe like; methanesulfonate works well. The reaction is conducted in thepresence of at least one equivalent of a base. Suitable bases includeinorganic bases, such as alkali metal (such as lithium, sodium orpotassium) carbonates and hydroxides, and organic bases, such astriethylamine, diisopropylethylamine and1,8-diazabicyclo[5.4.0]undec-7-ene. The reaction is generally conductedin a solvent, which can comprise alcohols, such as methanol and ethanol,halogenated alkanes, such as dichloromethane, aromatic solvents, such asbenzene, toluene and chlorobenzene, ethers, such as tetrahydrofuran, andpolar aprotic solvents, such as acetonitrile, such as such asacetonitrile, N,N-dimethylformamide, and the like. Alcohols and polaraprotic solvents are preferred for use with inorganic bases. Potassiumcarbonate as base and acetonitrile as solvent are preferred. Thereaction is generally conducted between about 0 and 150° C., with mosttypically between ambient temperature and 100° C. The product of Formula32b can be isolated by conventional techniques such as extraction. Theester of Formula 32b can then be converted to the carboxylic acid ofFormula 4d by the methods already described for the conversion ofFormula 32 to Formula 4d in Scheme 17. Further experimental details forthe method of Scheme 21 are illustrated in Example 16.

Compounds of Formula 38 can be prepared from compounds of Formula 33 asoutlined is Scheme 22.

wherein R¹³ is C₁-C₄ alkyl.

In this method, a hydrazine compound of Formula 33 is contacted with acompound of Formula 41 (a fumarate ester or maleate ester or a mixturethereof may be used) in the presence of a base and a solvent. The baseis typically a metal alkoxide salt, such as sodium methoxide, potassiummethoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide,lithium tert-butoxide, and the like. Greater than 0.5 equivalents ofbase versus the compound of Formula 33 should be used, preferablybetween 0.9 and 1.3 equivalents. Greater than 1.0 equivalents of thecompound of Formula 40 should be used, preferably between 1.0 to 1.3equivalents. Polar protic and polar aprotic organic solvents can beused, such as alcohols, acetonitrile, tetrahydrofuran,N,N-dimethylformamide, dimethyl sulfoxide and the like. Preferredsolvents are alcohols such as methanol and ethanol. It is especiallypreferred that the alcohol be the same as that making up the fumarate ormaleate ester and the alkoxide base. The reaction is typically conductedby mixing the compound of Formula 33 and the base in the solvent. Themixture can be heated or cooled to a desired temperature and thecompound of Formula 40 added over a period of time. Typically reactiontemperatures are between 0° C. and the boiling point of the solventused. The reaction may be conducted under greater than atmosphericpressure in order to increase the boiling point of the solvent.Temperatures between about 30 and 90° C. are generally preferred. Theaddition time can be as quick as heat transfer allows. Typical additiontimes are between 1 minute and 2 hours. Optimum reaction temperature andaddition time vary depending upon the identities of the compounds ofFormula 33 and Formula 40. After addition, the reaction mixture can beheld for a time at the reaction temperature. Depending upon the reactiontemperature, the required hold time may be from 0 to 2 hours. Typicalhold times are 10 to 60 minutes. The reaction mass then can be acidifiedby adding an organic acid, such as acetic acid and the like, or asinorganic acid, suck as hydrochloric acid, sulfuric acid and the like.Depending on the reaction conditions and the means of isolation, the—CO₂R¹³ function on the compound of Formula 38 may be hydrolyxed to—CO₂H; for example, the presence of water in the reaction mixture canpromote such hydrolysis. If the carboxylic acid (—CO₂H) is formed, itcan be converted back to —CO₂R¹³ wherein R¹³ is C₁-C₄ alkyl usingesterication methods well-known in the art. The desired product, acompound of Formula 38, can be isolated by methods known to thoseskilled in the art, such as crystallization, extraction or distillation.

It is recognized that some reagents and reaction conditions describedabove for preparing compounds of Formula I may not be compatible withcertain functionalities present in the intermediates. In theseinstances, the incorporation of protection/deprotection sequences orfunctional group interconversions into the synthesis will aid inobtaining the desired products. The use and choice of the protectinggroups will be apparent to one skilled in chemical synthesis (see, forexample, Greene, T. W.; Wuts P. G. M. Protective Groups in OrganicSynthesis, 2nd ed.; Wiley: New York, 1991). One skilled in the art willrecognize that, in some cases, after the introduction of a given reagentas it is depicted in any individual scheme, it may be necessary toperform additional routine synthetic steps not described in detail tocomplete the synthesis of compounds of Formula I. One skilled in the artwill also recognize that it may be necessary to perform a combination ofthe step illustrated in the above schemes in an order other than thatimplied by the particular sequence presented to prepare the compounds ofFormula I.

It is believed that one skilled in the art using the precedingdescription can prepare compounds of Formula I of the present inventionto its fullest extent. The following Examples are, therefore, to beconstrued as merely illustrative, and not limiting of me disclosure inany way whatsoever. Percentages are by weight except for chromatographicsolvent mixtures or where otherwise indicated. Parts and percentages forchromatographic solvent mixtures are by volume unless otherwiseindicated. ¹H NMR spectra are reported in ppm downfield fromtetramethylsilane; s means singlet, d means doublet, t means triplet, qmeans quartet, m means multiplet, dd means doublet of doublets, dt meansdoublet of triplets, br s means broad singlet.

Example 1 Preparation of 2-[1-Ethyl-3-trifluoromethylpyrazol-5-ylcarbomoyl]-3-methyl-N-(1-methylethyl)benzamide Step A: Preparation of3-Methyl-N-(1-methylethyl)-2-nitrobenzamide

A solution of 3-methyl-2-nitrobenzoic acid (2.00 g, 11.0 mmol) andtriethylamine (1.22 g, 12.1 mmol) in 25 mL of methylene chloride wascooled to 10° C. Ethyl chloroformate was carefully added and a solidprecipitate formed. After stirring for 30 minutes isopropylamine (0.94g, 16.0 mmol) was added and a homogeneous solution resulted. Thereaction was stirred for an additional hour, poured into water andextracted with ethyl acetate. The organic extracts were washed withwater, dried over magnesium sulfate and evaporated under reducedpressure to afford 1.96 g of the desired intermediate as a white solidmelting at 126-128° C.

¹H NMR (CDCl₃) δ 1.24 (d, 6H), 2.38 (s, 3H), 4.22 (m, 1H), 5.80 (br s,1H), 7.4 (m, 3H).

Step B: Preparation of 2-Amino-3-methyl-N-(1-methylethyl)benzamide

The 2-nitrobenzamide of Step A (1.70 g, 7.6 mmol) was hydrogenated over5% Pd/C in 40 mL of ethanol at 50 psi. When the uptake of hydrogenceased the reaction was filtered through Celite® diatomaceous filter aidand the Celite® was washed with ether. The filtrate was evaporated underreduced pressure to afford 1.41 g of the title compound as a solidmelting at 149-151° C.

¹H NMR (CDCl₃) δ 1.24 (dd, 6H), 2.16 (s, 3H), 4.25 (m, 1H), 5.54 (br s,2H), 5.85 (br s, 1H), 6.59 (t, 1H), 7.13 (d, 1H), 7.17 (d, 1H).

Step C: Preparation of 1-Ethyl-3-trifluoromethylpyrazol-5-yl carboxylicacid

To a mixture of 3-trifluoromethylpyrazole (5 g, 37 mmol) and powderedpotassium carbonate (10 g, 72 mmol) stirring in 30 mL ofN,N-dimethylformamide iodoethane (8 g, 51 mmol) was added dropwise.After a mild exotherm, the reaction was stirred overnight at roomtemperature. The reaction mixture was partitioned between 100 mL ofdiethyl ether and 100 mL of water. The ether layer was separated, washedwith water (3×) and brine, and dried over magnesium sulfate. Evaporationof solvent in vacuo gave 4 g of oil.

To 3.8 g of this oil stirring in 40 mL of tetrahydrofuran under nitrogenin a dry ice/acetone bath, 17 mL of a 2.5 M solution of n-butyllithiumin tetrahydrofuran (43 mmol) was added dropwise and the solution stirredfor 20 minutes at −78° C. An excess of gaseous carbon dioxide wasbubbled into the stirred solution at a moderate rate for 10 minutes.After addition of carbon dioxide, the reaction was allowed to slowlyreach room temperature and stirred overnight. The reaction mixture waspartitioned between diethyl ether (100 mL) and 0.5 N aqueous sodiumhydroxide (100 mL). The basic layer was separated and acidified withconcentrated hydrochloric acid to a pH of 2-3. The aqueous mixture wasextracted with ethyl acetate (100 mL) and the organic extract washedwith water and brine and dried over magnesium sulfate. The oily residue,which remained after evaporating the solvent in vacuo, was triturated toa solid from a small amount of 1-chlorobutane. After filtering anddrying, a slightly impure sample of1-ethyl-3-trifluoromethyl-pyrazol-5-yl carboxyilc acid (1.4 g) wasobtained as a broad-melting solid.

¹H NMR (CDCl₃) δ 1.51 (t, 3H), 4.68 (g, 2H), 7.23 (s, 1H), 9.85 (br s,1H).

Step D: Preparation of 2-[1-Ethyl-3-trifluoromethylpyrazol-5-ylcarbamoyl]-3-methyl-N-(1-methylethyl)benzamide

To a solution of 1-ethyl-3-trifluoromethyl-pyrazol-5-yl carboxyilc acid(i.e. the product of Step C) (0.5 g, 2.4 mmol) stirring in 20 mL ofmethylene chloride, oxalyl chloride (1.2 mL, 14 mmol) was added. Uponaddition of 2 drops of N,N-dimethylformamide, foaming and bubblingoccurred. The reaction mixture was heated at reflux for 1 hr as a yellowsolution. After cooling, the solvent was removed in vacuo and theresulting residue dissolved in 20 mL of tetrahydrofuran. To the stirredsolution, 2-amino-3-methyl-N-(1-methylethyl)benzamide (i.e. the productof Step B) (0.7 g, 3.6 mmol) was added followed by the dropwise additionof N,N-diisopropylethylamine (3 mL, 17 mmol). After stirring at roomtemperature overnight, the reaction mixture was partitioned betweenethyl acetate (100 mL) and 1 N aqueous hydrochloric acid (75 mL). Theseparated organic layer was washed with water and brine and dried overmagnesium sulfate. Evaporating in vacuo gave a white solid residue,which on purification by flash column chromatography on silica gel (2:1hexanes/ethyl acetate) afforded 0.5 g of the title compound, a compoundof the present invention, melting at 223-226° C.

¹H NMR (DMSO-d₆) δ 1.06 (d, 6H), 1.36 (t, 3H), 2.45 (s, 3H), 3.97 (m,1H), 4.58 ( q, 2H), 7.43-7.25 (m, 3H), 7.45 (s, 1H), 8.05 (d, 1H), 10.15(s; 1H).

Example 2 Preparation ofN-[2-Methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-phenyl-3-(trifluromethyl)-1H-pyrazole-5-carboxamideStep A: Preparation of 2-Methyl-1-phenyl-4-(trifluoromethyl)-1H-pyrazole

A solution of 1,1,1-trifluoropentane-2,4-dione (20.0 g, 0.130 mole) inglacial acetic acid (60 mL) was cooled to 7° C. using an ice/water bath.Phenylhydrazine (14.1 g, 0.130 mole) was added dropwise over a period of60 minutes. The reaction mass temperature increased to 15° C. during theaddition. The resulting orange solution was held under ambientconditions for 60 minutes. The bulk of the acetic acid was removed bystripping on a rotary evaporate at a bath temperature of 65° C. Theresidue was dissolved in methylene chloride (150 mL). The solution waswashed with aqueous sodium bicarbonate (3 g in 50 mL of water). Thepurple-red organic layer was separated, treated with activated charcoal(2 g) and MgSO₄, then filtered. Volatiles were removed on a rotaryevaporator. The crude product consisted of 28.0 g of a rose-colored oil,which contained ˜89% the desired product and 11%1-phenyl-5-(trifluoromethyl)-3-methylpyrazole.

¹H NMR (DMSO-d₆) δ 2.35 (s, 3H), 6.76 (s, 1H), 7.6-7.5 (m, 5H).

Step B: Preparation of1-Phenyl-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid

A sample of crude 2-methyl-1-phenyl-4-(trifluoromethyl)-1H-pyrazole(i.e., the product of Step A) (˜89%, 50.0 g, 0.221 mole) was mixed withwater (400 mL) and cetyltrimethylammonium chloride (4.00 g, 0.011 mole).The mixture was heated to 95° C. Potassium permanganate was added in 10equal portions, spaced at ˜8 minute intervals. The reaction mass wasmaintained at 95-100° C. during this period. After the last portion wasadded, the mixture was held for ˜15 minutes at 95-100° C., whereupon thepurple, permanganate color had been discharged. The reaction mass wasfiltered while hot (˜75° C.) through a 1-cm bed of Celite® diatomaceousfilter aid in a 150-mL coarse glass frit funnel. The filter cake waswashed with warm (˜50° C.) water (3×100 mL). The combined filtrate andwashings were extracted with ether (2×100 mL) to remove a small amountof yellow, water-insoluble material. The aqueous layer was purged withnitrogen to remove residual ether. The clear, colorless alkalinesolution was acidified by adding concentrated hydrochloric acid dropwiseuntil the pH reacted ˜1.3 (28 g, 0.28 mole). Gas evolution was vigorousduring the first two-thirds of the addition. The product was collectedvia filtration, washed with water (3×40 mL), then dried overnight, at55° C. in vacuo. The product consisted of 11.7 g of a white, crystallinepowder, which was essentially pure based upon ¹H NMR.

¹H NMR (CDCl₃) δ 7.33 (s, 1H), 7.4-7.5 (m, 5H)

Step C: Preparation of1-Phenyl-3-(trifluoromethyl)-1H-pyrazole-5-carbonyl chloride

A sample of crude 1-phenyl-3-(trifluoromethyl)pyrazole-5-carboxylic acid(i.e. the product of Step B) (4.13 g, 16.1 mmol) was dissolved inmethylene chloride (45 mL). The solution was treated with oxalylchloride (1.80 mL, 20.6 mmol), followed by N,N-dimethylformamide (0.010mL, 0.13 mmol). Off-gassing began shortly after adding theN,N-dimethylformamide catalyst. The reaction mixture was stirred for ˜20minutes under ambient conditions, then was heated to reflux for a periodof 35 minutes. Volatiles were removed by stripping the reaction mixtureon a rotary evaporator at a bath temperature of 55° C. The productconsisted of 4.43 g of a light-yellow oil. The only imparity observed by¹H NMR was N,N-dimethylformamide.

¹H NMR (CDCl₃) δ 7.40 (m, 1H), 7.42 (s, 1H), 7.50-7.53 (m, 4H).

Step D: Preparation ofN-[2-Methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-phenyl-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide

A sample of 3-methylisatoic anhydride (0.30 g, 1.7 mmol) partiallydissolved in pyridine (4.0 mL) was treated with1-phenyl-3-(trifluoromethylpyrazole)-5-carboxyl chloride (i.e. theproduct of Step C) (0.55 g, 1.9 mmol). The mixture was heated to ˜95° C.for a period of 2 hours. The resulting orange solution was cooled to 29°C., then was treated with isopropylamine (1.00 g, 16.9 mmol). Thereaction mass exothermically warmed to 39° C. It was further heated to55° C. for a period of 30 minutes, whereupon much precipitate formed.The reaction mass was dissolved in dichloromethane (150 mL). Thesolution was washed with aqueous acid (5 mL of conc. HCl in 45 mL ofwater), then with aqueous base (2 g sodium carbonate in 50 mL of water).The organic layer was dried over MgSO₄, filtered, then concentrated on arotary evaporator. Upon reduction to ˜4 mL, product crystals had formed.The slurry was diluted with ˜10 mL of ether, whereupon more productprecipitated. The product was isolated by filtration, washed with ether(2×10 mL), then washed with water (2×50 mL). The wet cake was dried for30 minutes at 70° C. in vacuo. The product, a compound of the presentinvention, consisted of 0.52 g of an off-white powder melting at260-262° C.

¹H NMR (DMSO-d₆) δ 1.07 (d, 6H), 2.21 (s, 3H), 4.02 (octet, 1H), 7.2-7.4(m, 3H), 7.45-7.6 (m, 6H), 8.10 (d, 1H) 10.31 (s, 1H).

Example 3 Preparation ofN-[2-Methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-3-(trifluoromethyl)-1-[3-(trifluoromethyl)-2-pyridinyl]-1H-pyrazole-5-carboxamideStep A: Preparation of3-Trifluoromethyl-2-[3-(trifluoromethyl)-1H-pyrazol-1-yl]pyridine

A mixture of 2-chloro-3-trifluoromethylpyridine (3.62 g, 21 mmol),3-trifluoro-methylpyrazole (2.7 g, 20 mmol), and potassium carbonate(6.0 g, 43 mmol) were heated at 100° C. for 18 h. The cooled reactionmixture was added to ice/water (100 mL). The mixture was extracted twicewith ether (100 mL) and the combined ether extracts were washed twicewith water (100 mL). The organic layer was dried with magnesium sulfateand concentrated to an oil. Chromatography on silica gel withhexanes:ethyl acetate (8:1 to 4:1) as eluent gave the title compound(3.5 g) as an oil.

¹H NMR (CDCl₃) δ 6.75 (m, 1H), 7.5 (m, 1H), 8.2 (m, 2H), 8.7 (m, 1H).

Step B: Preparation of3-(Trifluoromethyl)-1-[3-(trifluoromethyl)-2-pyridinyl]-1H-pyrazole-5-carboxylicacid

A mixture of the title compound of Example 3, Step A (3.4 g, 13 mmol)was dissolved in tetrahydrofuran (30 mL) and cooled to −70° C. Lithiumdiisopropylamide (2 N in heptane/tetrahydrofuran, (Aldrich) 9.5 mL, 19mmol) was added and the resulting dark mixture was stirred for 10minutes. Dry carbon dioxide was bubbled through the mixture for 15minutes. The mixture was allowed to warm to 23° C. and treated withwater (50 mL) and 1 N sodium hydroxide (10 mL). The aqueous mixture wasextracted with ether (100 mL) and then ethyl acetate (100 mL). Theaqueous layer was acidified with 6 N hydrochloric acid to pH 1-2 andextracted twice with dichloromethane. The organic layer was dried withmagnesium sulfate and concentrated to give the title compound (15 g).

¹H NMR (CDCl₃) δ 7.6 (m, 1H), 7.95 (m, 1H), 8.56 (m, 1H), 8.9 (m, 1H)14.2 (br, 1H)

Step C: Preparation ofN-[2-Methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-3-(trifluoromethyl)-1-[3-(trifluoromethyl)-2-pyridinyl]-1H-pyrazole-5-carboxamide

A mixture of the title compound of Example 3, Step B (0.54 g, 1.1 mmol),the title compound from Example 1, Step B (0.44 g, 2.1 mmol) and BOPchloride (bis(2-oxo-oxazolidinyl)phosphinyl chloride, 0.54 g, 2.1 mmol)in acetonitrile (13 mL) was treated with triethylamine (0.9 mL). Themixture was shaken in a closed scintillation vial for 18 h. The reactionwas partitioned between ethyl acetate (100 mL) and 1 N hydrochloricacid. The ethyl acetate layer was washed successively with hydrochloricacid (50 mL), 1 N sodium hydroxide (50 mL) and saturated sodium chloridesolution (50 mL). The organic layer was dried over magnesium sulfate andconcentrated. The residue was subjected to column chromatography onsilica gel with hexanes/ethyl acetate (5:1 to 3:1) as eluent. The titlecompound (0.43 g), a compound of the present invention, was isolated asa white solid. m.p. 227-230° C.

¹H NMR (CDCl₃) δ 1.2 (m, 6H), 4.15 (m, 1H), 5.9 (br d, 1H), 7.1 (m, 1H),7.2 (m, 2H), 7.4 (s, 1H), 7.6 (m, 1H), 8.15 (m, 1H), 8.74 (m, 1H), 10.4(br, 1H).

Example 4 Preparation of1-(3-Chloro-2-pyridinyl)-N-[2-methyl-6-[[(1-methylethyl)amino]carbonyl]-phenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamideStep A: Preparation of3-Chloro-2-[3-(trifluoromethyl)-1H-pyrazol-1-yl]pyridine

To a mixture of 2,3-dichloropyridine (99.0 g, 0.67 mol) and3-(trifluoromethyl)-pyrazole (83 g, 0.61 mol) is dryN,N-dimethylformamide (300 mL) was added potassium carbonate (166.0 g,1.2 mol) and the reaction was then heated to 110-125° C. over 48 hours.The reaction was cooled to 100° C. and filtered through Celite®diatomaceous filter aid to remove solids. N,N-Dimethylformamide andexcess dichloropyridine were removed by distillation at atmosphericpressure. Distillation of the product at reduced pressure (b.p. 139-141°C., 7 mm) afforded the desired intermediate as a clear yellow oil (113.4g).

¹H NMR (CDCl₃) δ 6.78 (s, 1H), 7.36 (t, 1H), 7.93 (d, 1H), 8.15 (s, 1H),8.45 (d, 1H).

Step B: Preparation of1-(3-Chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylicacid

To a solution of3-chloro-2-[3-(trifluoromethyl)-1H-pyrazol-1-yl]pyridine (i.e. theproduct of Step A) (105.0 g, 425 mmol) in dry tetrahydrofuran (700 mL)at −75° C. was added via cannula a −30° C. solution of lithiumdiisopropylamide (425 mmol) in dry tetrahydrofuran (300 mL). The deepred solution was stirred for 15 minutes, after which time carbon dioxidewas bubbled through at −63° C. until the solution became pale yellow andthe exothermicity ceased. The reaction was stirred for an additional 20minutes and then quenched with water (20 mL). The solvent was removedunder reduced pressure, and the reaction mixture partitioned betweenether and 0.5 N aqueous sodium hydroxide solution. The aqueous extractswere washed with ether (3×), filtered through Celite® diatomaceousfilter aid to remove residual solids, and then acidified to a pH ofapproximately 4, at which point an orange oil formed. The aqueousmixture was stirred vigorously and additional acid was added to lowerthe pH to 2.5-3. The orange oil congealed into a granular solid, whichwas filtered, washed successively with water and 1 N hydrochloric acid,and dried under vacuum at 50° C. to afford the title product as anoff-white solid (130 g). Product from another run following similarprocedures melted at 175-176° C.)

¹H NMR (DMSO-d₆) δ 7.61 (s, 1H), 7.76 (dd, 1H), 8.31 (d, 1H), 8.60 (d,1H).

Step C: Preparation of 8-Methyl-2H-3,1-benzoxazine-2,4(1H)-dione

To a solution of 2-amino-3-methylbenzoic acid (6 g) in dry 1,4-dioxane(50 mL) was added stepwise a solution of trichloromethyl chloroformate(8 mL) in dry 1,4-dioxane (25 mL), with ice-water cooling to keep thereaction temperature below 25° C. A white precipitate began to formduring the addition. The reaction mixture was stirred at roomtemperature overnight. The precipitated solids were removed byfiltration and washed with 1,4-dioxane (2×20 mL) and hexane (2×15 mL)and air-dried to yield 6.51 g of off-white solid.

¹H NMR (DMSO-d₆) δ 2.33 (s, 3H), 7.18 (t, 1H), 7.59 (d, 1H), 7.78 (d,1H), 11.0 (br s, 1H).

Step D: Preparation of2-[1-(3-Chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benozoxazin-4-one

To a suspension of the carboxylic acid product prepared as in Step B(146 g, 500 mmol) in dichloromethane (approximately 2 L) was addedN,N-dimethylformamide (20 drops) and oxalyl chloride (67 mL, 750 mmol)in approximately 5-mL portions over approximately 2 h. Vigorous gasevolution occurred during the addition. The reaction mixture was stirredat room temperature overnight. The reaction mixture was concentrated invacuo to provide the crude acid chloride as an opaque orange mixture.This material was taken up is dichloromethane, filtered to remove somesolids and then reconcentrated and used without further purification.The crude acid chloride was dissolved in acetonitrile (250 mL) and addedto a suspension of the product from Step C in acetonitrile (400 mL).Pyridine (250 mL) was added, the mixture was stirred for 15 min at roomtemperature, then warmed to reflux for 3 h. The resulting mixture wascooled to room temperature and stirred overnight to provide a solidmass. Additional acetonitrile was added and the mixture was mixed toform a thick slurry. The solids were collected and washed with coldacetonitrile. The solids were air-dried and the dried in vacuo at 90° C.for 5 h to yield 144.8 g of fluffy white solid.

¹H NMR (CDCl₃) δ 1.84 (s, 3H), 7.4 (t, 1H), 7.6 (m, 3H), 8.0 (dd, 1H),8.1 (s, 1H), 8.6 (d, 1H).

Step E: Preparation of1-(3-Chloro-2-pyridinyl)-N-[2-methyl-6-[[(1-methylethyl)-amino]carbonyl]phenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide

To a suspension of the benzoxazinone product of Step D (124 g, 300 mmol)in dichloromethane (500 mL) was added dropwise isopropylamine (76 mL,900 mmol) at room temperature. The temperature of the reaction mixturerose and the suspension thinned during the addition. The reactionmixture was then warmed to reflux for 1.5 h. A new suspension formed.The reaction mixture was cooled to room temperature and diethyl ether(1.3 L) was added and the mixture stirred at room temperature overnight.The solids were collected and washed with ether. The solids wereair-dried and then dried in vacuo at 90° C. for 5 h to yield 122 g ofthe title compound, a compound of the present invention, as a fluffywhite solid, melting at 194-196° C.

¹H NMR (CDCl₃) δ 1.23 (d, 6H), 2.21 (s, 3H) 4.2 (m, 1H) 5.9 (d, 1H), 7.2(t, 1H), 7.3 (m, 2H), 7.31 (s, 1H), 7.4 (m, 1H), 7.8 (d, 1H), 8.5 (d,1H), 10.4 (s, 1H).

Example 5 Alternate Preparation of1-(3-chloro-2-pyridinyl)-N-[2-methyl-6-[[(1-methylethyl)amino]-carbonyl]phenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide

To a solution of the carboxylic acid product prepared as in Example 4,Step B (28 g, 96 mmol) in dichloromethane (240 mL) was addedN,N-dimethylformamide (12 drops) and oxalyl chloride (15.8 g, 124 mmol).The reaction mixture was stirred at room temperature until gas evolutionceased (approximately 1.5 h). The reaction mixture was concentrated invacuo to provide the crude acid chloride as an oil that was used withoutfurther purification. The crude acid chloride was dissolved inacetonitrile (95 mL) and added to a solution of the benzoxazin-2,4-dioneprepared as in Example 4, Step C in acetonitrile (95 mL). The resultingmixture was stirred at room temperature (approximately 30 min.).Pyridine (95 mL) was added and the mixture heated to about 90° C.(approximately 1 h). The reaction mixture was cooled to about 35° C. andisopropylamine (25 mL) was added. The reaction mixture exothermicallywarmed during the addition and then was maintained at about 50° C.(approximately 1 h). The reaction mixture was then poured into ice waterand stirred. The resulting precipitate was collected by filtrationwashed with water and dried in vacuo overnight to provide 37.5 g of thetitle compound, a compound of the present invention, as a tan solid.

¹H NMR (CDCl₃) δ 1.23 (d, 6H), 2.21 (s, 3H), 4.2 (m, 1H), 5.9 (d, 1H),7.2 (t, 1H), 7.3 (m, 2H), 7.31 (s, 1H), 7.4 (m, 1H), 7.8 (d, 1H), 8.5(d, 1H), 10.4 (s, 1H).

Example 6 Preparation ofN-[4-chloro-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamideStep A: Preparation of 2-Amino-3-methyl-5-chlorobenzoic acid

To a solution of 2-amino-3-methylbenzoic acid (Aldrich, 15.0 g, 99.2mmol) in N,N-dimethylformamide (50 mL) was added N-chlorosuccinimide(13.3 g, 99.2 mmol) and the reaction mixture was heated to 100° C. for30 minutes. The heat was removed, the reaction was cooled to roomtemperature and let stand overnight. The reaction mixture was thenslowly poured into ice-water (250 mL) to precipitate a white solid. Thesolid was filtered and washed four times with water and then taken up inethyl acetate (900 mL). The ethyl acetate solution was dried overmagnesium sulfate, evaporated under reduced pressure and the residualsolid was washed with ether to afford the desired intermediate as awhite solid (13.9 g).

¹H NMR (DMSO-d₆) δ 2.11 (s, 3H), 7.22 (s, 1H), 7.55 (s, 1H).

Step B: Preparation of3-chloro-2-[3-(trifluoromethyl)-1H-pyrazol-1-yl]-pyridine

To a mixture of 2,3-dichloropyridine (99.0 g, 0.67 mol) and3-trifluoromethyl pyrazole (83 g, 0.61 mol) in dry N,N-dimethylformamide(300 mL) was added potassium carbonate (166.0 g, 1.2 mol) and thereaction was then heated to 110-125° C. over 48 hours. The reaction wascooled to 100° C. and filtered through Celite® diatomaceous filter aidto remove solids. N,N-Dimethylformamide and excess dichloropyridine wereremoved by distillation at atmospheric pressure. Distillation of theproduct at reduced pressure (b.p. 139-141° C., 7 mm) afforded the titlecompound as a clear yellow oil (113.4 g).

¹H NMR (CDCl₃) δ 6.78 (s, 1H), 7.36 (t, 1H), 7.93 (d, 1H), 8.15 (s, 1H),8.45 (d, 1H).

Step C: Preparation of1-(3-Chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylicacid

To a solution of the pyrazole product from Step B (10.10 g, 425 mmol) indry tetrahydrofuran (700 mL) at −75° C. was added via cannula a −30° C.solution of lithium diisopropylamide (425 mmol) in dry tetrahydrofuran(300 mL). The deep red solution was stirred for 15 minutes, after whichtime carbon dioxide was bubbled through at −63° C. until the solutionbecame pale yellow and the exothermicity ceased. The reaction wasstirred for an additional 20 minutes and then quenched with water (20mL). The solvent was removed under reduced pressure, and the reactionmixture was partitioned between ether and 0.5 N aqueous sodium hydroxidesolution. The aqueous extracts were washed with ether (3×), filteredthrough Celite® diatomaceous filter aid to remove residual solids, andthen acidified to a pH of approximately 4, at which point an orange oilformed. The aqueous mixture was stirred vigorously and additional acidwas added to lower the pH to 2.5-3. The orange oil congealed into agranular solid, which was filtered, washed successively with water and 1N hydrochloric acid, and dried under vacuum at 50° C. to afford thetitle product as an off-white solid (130 g). (Product from another runfollowing similar procedure melted at 175-176° C.)

¹H NMR (DMSO-d₆) δ 7.61 (s, 1H), 7.76 (dd, 1H), 8.31 (d, 1H), 8.60 (d,1H).

Step D: Preparation of6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazin-4-one

To a solution of methanesulfonyl chloride (2.2 mL, 28.3 mmol) inacetonitrile (75 mL) was added dropwise a mixture of the carboxylic acidproduct from Step C (7.5 g, 27.0 mmol) and triethylamine (3.75 mL, 27.0mmol) in acetonitrile (75 mL) at 0-5° C. The reaction temperature wasthen maintained at 0° C. throughout successive addition of reagents.After stirring for 20 minutes, 2-amino-3-methyl-5-chlorobenzoic acidfrom Step A (5.1 g, 27.0 mmol) was added and stirring was continued foran additional 5 minutes. A solution of triethylamine (7.5 mL, 54.0 mmol)in acetonitrile (15 mL) was then added dropwise, and the reactionmixture was stirred 45 minutes, followed by the addition ofmethanesulfonyl chloride (2.2 mL, 28.3 mmol). The reaction mixture wasthen warmed to room temperature and stirred overnight. Approximately 75mL of water was then added to precipitate 5.8 g of a yellow solid. Anadditional 1 g of product was isolated by extraction from the filtrateto provide a total of 6.8 g of the title compound as a yellow solid.

¹H NMR (CDCl₃) δ 1.83 (s, 3H), 7.50 (s, 1H), 7.53 (m, 2H), 7.99 (m, 2H),8.58 (d, 1H).

Step E: Preparation ofN-[4-Chloro-2-methyl-6-[[(1-methylethyl)amino]carbonyl]-phenyl]-1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide

To a solution of the benzoxazinone product of Step D (5.0 g, 11.3 mmol)in tetrahydrofuran (35 mL) was added dropwise isopropylamine (2.9 mL,34.0 mmol) in tetrahydrofuran (10 mL) at room temperature. The reactionmixture was then warmed until all solids had dissolved and stirred anadditional five minutes, at which point thin layer chromatography onsilica gel confirmed completion of the reaction. The tetrahydrofuransolvent was evaporated under reduced pressure, and the residual solidwas purified by chromatography on silica gel, followed by triturationwith ether/hexane to afford the title compound, a compound of thepresent invention, as a solid (4.6 g), melting at 195-196° C.

¹H NMR (CDCl₃) δ 1.21 (d, 6H), 2.17 (s, 3H), 4.16 (m, 1H), 5.95 (br d,1H), 7.1-7.3 (m, 2H) 7.39 (s, 1H), 7.4 (m, 1H), 7.84 (d, 1H), 8.50 (d,1H), 10.24 (br s, 1H).

Example 7 Preparation ofN-[4-Chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide

To a solution of the benzoxazinone product of Example 6, Step D (4.50 g,10.18 mmol) is tetrahydrofuran (THF; 70 mL) was added methylamine (2.0 Msolution in THF, 15 mL, 30.0 mmol) dropwise and the reaction mixture wasstirred at room temperature for 5 minutes. The tetrahydrofuran solventwas evaporated under reduced pressure and the residual solid waspurified by chromatography on silica gel to afford 4.09 g of the titlecompound, a compound of the present invention, as a white solid meltingat 185-186° C.

¹H NMR (DMSO-d₆) δ 2.17 (s, 3H), 2.65 (d, 3H), 7.35 (d, 1H), 7.46 (dd,1H), 7.65 (dd, 1H), 7.74 (s, 1H), 8.21 (d, 1H), 8.35 (br q, 1H), 8.74(d, 1H) 10.39 (s, 1H).

Example 8 Preparation of3-Chloro-N-[4-chloro-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamideStep A: Preparation of 3-Chloro-N,N-dimethyl-1H-pyrazole-1-sulfonamide

To a solution of N-dimethylsulfamoylpyrazole (188.0 g, 1.07 mol) in drytetrahydrofuran (1500 mL) at ˜78° C. was added dropwise a solution of2.5 M n-butyllithium (472 mL, 1.18 mol) in hexane while maintaining thetemperature below −65° C. Upon completion of the addition the reactionmixture was maintained at −78° C. for an additional 45 minutes, afterwhich time a solution of hexachloroethane (279 g, 1.18 mol) intetrahydrofuran (120 mL) was added dropwise. The reaction mixture wasmaintained for an hour at −78° C., warmed to −20° C. and then quenchedwith water (1 L). The reaction mixture was extracted with methylenechloride (4×500 mL); the organic extracts ware dried over magnesiumsulfate and concentrated. The crude product was further purified bychromatography on silica gel using methylene chloride as eluent toafford the title product compound as a yellow oil (160 g).

¹H NMR (CDCl₃) δ 3.07 (d, 6H), 6.33 (s, 1H), 7.61 (s, 1H).

Step B: Preparation of 3-Chloropyrazole

To trifluoroacetic acid (290 mL) was added dropwise the chloropyrazoleproduct (160 g) from Step A, and the reaction mixture was stirred atroom temperature for 1.5 hours and then concentrated at reducedpressure. The residue was taken up in hexane, insoluble solids werefiltered off, and the hexane was concentrated to afford the crudeproduct as an oil. The crude product was further purified bychromatography on silica gel using ether/hexane (40:60) as eluent toafford the title product as a yellow oil (64.44 g).

¹H NMR (CDCl₃) δ 6.39 (s, 1H), 7.66 (s, 1H), 9.6 (br s, 1H).

Step C: Preparation of 3-Chloro-2-(3-chloro-1H-pyrazol-1-yl)pyridine

To a mixture of 2,3-dichloropyridine (92.60 g, 0.629 mol) and3-chloropyrazole (i.e. the product of Step B) (64.44 g, 0.629 mol) inN,N-dimethylformamide (400 mL) was added potassium carbonate (147.78 g1.06 mol), and the reaction mixture was then heated to 100° C. for 36hours. The reaction mixture was cooled to room temperature and slowlypoured into ice water. The precipitated solids were filtered and washedwith water. The solid filter cake was taken up in ethyl acetate, driedover magnesium sulfate and concentrated. The crude solid waschromatographed on silica gel using 20% ethyl acetate/hexane as eluentto afford the title product as a white solid (39.75 g).

¹H NMR (CDCl₃) δ 6.43 (s, 1H), 7.26 (m, 1H), 7.90 (d, 1H), 8.09 (s, 1H),8.41 (d, 1H).

Step D: Preparation of3-Chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid

To a solution of the pyrazole product from Step C (39.75 g, 186 mmol) indry tetrahydrofuran (400 mL) at −78° C. was added dropwise a solution of2.0 M lithium diisopropylamide (93 mL, 186 mmol) in tetrahydrofuran.Carbon dioxide was bubbled through the amber solution for 14 minutes,after which time the solution became pale brownish-yellow. The reactionwas made basic with 1 N aqueous sodium hydroxide solution and extractedwith ether (2×500 mL). The aqueous extracts were acidified with 6 Nhydrochloric acid and extracted with ethyl acetate (3×500 mL). The ethylacetate extracts were dried over magnesium sulfate and concentrated toafford the title product as an off-white solid (42.96 g). (Product fromanother run following similar procedure melted at 198-199° C.)

¹H NMR (DMSO-d₆) δ 6.99 (s, 1H), 7.45 (m, 1H), 7.93, (d, 1H), 8.51 (d,1H).

Step E: Preparation of6-Chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazin-4-one

To a solution of methanesulfonyl chloride (6.96 g, 61.06 mmol) inacetonitrile (1.50 mL) was added dropwise a mixture of the carboxylicacid product from Step D (15.0 g, 58.16 mmol) and trietheylamine (5.88g, 58.16 mmol) in acetonitrile (150 mL) at −5° C. The reaction mixturewas then stirred for 30 minutes at 0° C. Then,2-amino-3-methyl-5-chlorobenzoic acid from Example 6, Step A (10.79 g,58.16 mmol) was added, and stirring was continued for an additional 10minutes. A solution of triethylamine (11.77 g, 116.5 mmol) inacetonitrile was then added dropwise while keeping the temperature below10° C. The reaction mixture was stirred 60 minutes at 0° C., and thenmethanesulfonyl chloride (6.96 g, 61.06 mmol) was added. The reactionmixture was then warmed to room temperature and stirred for anadditional 2 hours. The reaction mixture was then concentrated, and thecrude product was chromatographed on silica gel using methylene chlorideas eluent to afford the title product as a yellow solid (9.1 g).

¹H NMR (CDCl₃) δ 1.81 (s, 3H), 7.16 (s, 1H), 7.51 (m, 2H), 7.98 (d, 2H),8.56 (d, 1H).

Step F: Preparation of3-chloro-N-[4-chloro-2-methyl-6-[[(1-methylethyl)amino]-carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide

To a solution of the benzoxazinone product of Step B (6.21 g, 15.21mmol) in tetrahydrofuran (100 mL) was added isopropylamine (4.23 g,72.74 mmol) and the reaction mixture was then heated to 60° C., stirredfor 1 hour and then cooled to room temperature. The tetrahydrofuransolvent was evaporated under reduced pressure, and the residual solidwas purified by chromatography on silica gel to afford the titlecompound, a compound of the present invention, as a white solid (5.05 g)melting at 173-175° C.

¹H NMR (CDCl₃) δ 1.23 (d, 6H), 2.18 (s, 3H), 4.21 (m, 1H), 5.97 (d, 1H),7.01 (m, 1H), 7.20 (s, 1H), 7.24 (s, 1H), 7.41 (d, 1H), 7.83 (d, 1H),8.43 (d, 1H), 10.25 (br s, 1H).

Example 9 Preparation of3-Chloro-N-[4-chloro-2-methyl-6-[(1-methylethylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide

To a solution of the benzoxazinone product of Example 8, Step E (6.32 g,15.47 mmol) in tetrahydrofuran (50 mL) was added methylamine (2.0 Msolution in THF, 38 mL, 77.38 mmol), and the reaction mixture was heatedto 60° C., stirred for 1 hour and then cooled to room temperature. Thetetrahydrofuran solvent was evaporated under reduced pressure, and theresidual solid was purified by chromatography on silica gel to affordthe title compound, a compound of the present invention, as a whitesolid (4.57 g) melting at 225-226° C.,

¹H NMR (CDCl₃) δ 2.15 (s, 3H), 2.93 (s, 3H), 6.21 (d, 1H), 7.06 (s, 1H),7.18 (s, 1H), 7.20 (s, 1H), 7.42 (m, 1H), 7.83 (d, 1H), 8.42 (d, 1H),10.08 (br s, 1H).

Example 10 Preparation of3-Bromo-N-[4-chloro-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamideStep A: Preparation of 3-Bromo-N,N-dimethyl-1H-pyrazole-1-sulfonamide

To a solution of N-dimethylsulfamoylpyrazole (44.0 g, 0.251 mol) in drytetrahydrofuran (500 mL) at −78° C. was added dropwise a solution ofn-butyllithium (2.5 M in hexane, 105.5 mL, 0.264 mol) while maintainingthe temperature below −60° C. A thick solid formed during the addition.Upon completion of the addition the reaction mixture was maintained foran additional 15 minutes, after which time a solution of1,2-dibromo-tetrachloroethane (90 g, 0.276 mol) in tetrahydrofuran (150mL) was added, dropwise while maintaining the temperature below −70° C.The reaction mixture turned a clear orange; stirring was continued foran additional 15 minutes. The −78° C. bath was removed and the reactionwas quenched with water (600 mL). The reaction mixture was extractedwith methylene chloride (4×), and the organic extracts were dried overmagnesium sulfate and concentrated. The crude product was furtherpurified by chromatography on silica gel using methylene chloride/hexane(50:50) as eluent to afford the title product as a clear colorless oil(57.04 g).

¹H NMR (CDCl₃) δ 3.07 (d, 6H), 6.44 (m, 1H), 7.62 (m, 1H).

Step B: Preparation of 3-Bromopyrazole

To trifluoroacetic acid (70 mL) was slowly added the bromopyrazoleproduct (57.04 g) from Step A. The reaction mixture was stirred at roomtemperature for 30 minutes and then concentrated at reduced pressure.The residue was taken up in hexane, insoluble solids were filtered off,and the hexane was evaporated to afford the crude product as an oil. Thecrude product was further purified by chromatography on silica gel usingethyl acetate/dichloromethane (10:90) as eluent to afford an oil. Theoil was taken up in dichloromethane, neutralized with aqueous sodiumbicarbonate solution, extracted with methylene chloride (3×), dried overmagnesium sulfate and concentrated to afford the title product as awhite solid (25.9 g), m.p. 61-64° C.

¹H NMR (CDCl₃) δ 6.37 (d, 1H), 7.59 (d, 1H), 12.4 (br s, 1H).

Step C: Preparation of 2-(3-Bromo-1H-pyrazol-1-yl)-3-chloropyridine

To a mixture of 2,3-dichloropyridine (27.4 g, 185 mmol) and3-bromopyrazole (i.e. the product of Step B) (25.4 g, 176 mmol) in dryN,N-dimethylformamide (88 mL) was added potassium carbonate (48.6 g, 352mmol), and the reaction mixture was heated to 125° C. for 18 hours. Thereaction mixture was cooled to room temperature and poured into icewater (800 mL). A precipitate formed. The precipitated solids werestirred for 1.5 hrs, filtered and washed with water (2×100 mL). Thesolid fiber cake was taken up in methylene chloride and washedseparately with water, 1 N hydrochloric acid, saturated aqueous sodiumbicarbonate solution, and brine. The organic extracts were then driedover magnesium sulfate and concentrated to afford 39.9 g of a pink sold.The crude solid was suspended in hexane and stirred vigorously for 1 hr.The solids were filtered, washed with hexane and dried to afford thetitle product as an off-white powder (30.4 g) determined to be >94% pureby NMR. This material was used without further purification in Step D.

¹H NMR (CDCl₃) δ 6.52 (s, 1H), 7.30 (dd, 1H), 7.92 (d, 1H), 8.05 (s,1H), 8.43 (d, 1H).

Step D: Preparation of3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid

To a solution of the pyrazole product from Step C (30.4 g, 118 mmol) indry tetrahydrofuran (250 mL) at −76° C. was added dropwise a solution oflithium diisopropyl amide (118 mmol) in tetrahydrofuran at such a rateas to maintain the temperature below −71° C. The reaction mixture wasstirred for 15 minutes at −76° C., and carbon dioxide was then bubbledthrough for 10 minutes, causing warming to −57° C. The reaction mixturewas warmed to −20° C. and quenched with water. The reaction mixture wasconcentrated and then taken up in water (1 L) and ether (500 mL), andthen aqueous sodium hydroxide solution (1 N, 20 mL) was added. Theaqueous extracts were washed with ether and acidified with hydrochloricadd. The precipitated solids were filtered, washed with water and driedto afford the title product as a tan solid (27.7 g). (Product fromanother run following similar procedure melted at 200-201° C.)

¹H NMR (DMSO-d₆) δ 7.25 (s, 1H), 7.68 (dd, 1H), 8.24 (d, 1H), 8.56 (d,1H).

Step E: Preparation of2-[3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazin-4-one

A procedure analogous to that of Example 6, Step D was used to convertthe pyrazolecarboxylic acid product from Example 10, Step B (1.5 g, 4.96mmol) and 2-amino-3-methyl-5-chlorobenzoic acid (0.92 g, 4.96 mmol) tothe title product as a solid (1.21 g).

¹H NMR (CDCl₃) δ 2.01 (s, 3H), 7.29 (s, 1H), 7.42 (d, 1H), 7.95 (d, 1H),8.04 (m, 1H), 8.25 (s, 1H), 8.26 (d, 1H).

Step F: Preparation of3-Bromo-N-[4-chloro-2-methyl-6-[[(1-methylethyl)amino]-carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide

To a solution of the benzoxazinone product of Step E (0.20 g, 0.44 mmol)in tetrahydrofuran was added isopropylamine (0.122 mL, 1.42 mmol), andthe reaction mixture was heated to 60° C. for 90 minutes and then cooledto room temperature. The tetrahydrofuran solvent was evaporated underreduced pressure, and the residual solid was triturated with ether,filtered, and dried to afford the title compound, a compound of thepresent invention, as a solid (150 mg), m.p. 159-161° C.

¹H NMR (CDCl₃) δ 1.22 (d, 6H), 2.19 (s, 3H), 4.21 (m, 1H), 5.99 (m, 1H),7.05 (m, 1H), 7.22 (m, 2H), 7.39 (m, 1H), 7.82 (d, 1H), 8.41 (d, 1H).

Example 11 Preparation of3-Bromo-N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide

To a solution of the benzoxazinone product of Example 10, Step E (0.20g, 0.44 mmol) in tetrahydrofuran was added methylamine (2.0 M solutionin THF, 0.514 mL, 1.02 mmol), and the reaction mixture was heated to 60°C. for 90 minutes and then cooled to room temperature. Thetetrahydrofuran solvent was evaporated under reduced pressure, and theresidual solid was triturated with ether, filtered, and dried to affordthe title compound, a compound of the present invention, as a solid (40mg), m.p. 162-164° C.

¹H NMR (CDCl₃) δ 2.18 (s, 3H), 2.95 (s, 3H), 6.21 (m, 1H), 7.10 (s, 1H),7.24 (m, 2H), 7.39 (m, 1H), 7.80 (d, 1H), 8.45 (d, 1H).

The following Example 12 illustrates an alternative preparation of3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid, whichcan be used to prepare, for example,3-chloro-N-[4-chloro-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamideand3-chloro-N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide,by further steps illustrated in Examples 8 and 9.

Example 12 Preparation of3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid Step A:Preparation of Ethyl2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolidinecarboxylate (alternativelynamed ethyl 1-(3-chloro-2-pyridinyl)-3-pyrazolidinone-5-carboxylate)

A 2-L four-necked flask equipped with a mechanical stirrer, thermometer,addition funnel, reflux condenser, and nitrogen inlet was charged withabsolute ethanol (250 mL) and an ethanolic solution of sodium ethoxide(21%, 190 mL, 0.504 mol). The mixture was heated to reflux at about 83°C. It was then treated with 3-chloro-2(1H)-pyridinone hydrazone (68.0 g,0.474 mol). The mixture was re-heated to reflux over a period of 5minutes. The yellow slurry was then treated dropwise with diethylmaleate (88.0 mL, 0.544 mol) over a period of 5 minutes. The reflux rateincreased markedly during the addition. By the end of the addition allof the starting material had dissolved. The resulting orange-redsolution was held at reflux for 10 minutes. After being cooled to 65°C., the reaction mixture was treated with glacial acetic acid (50.0 mL,0.873 mol). A precipitate formed. The mixture was diluted with water(650 mL), causing the precipitate to dissolve. The orange solution wascooled in an the bath. Product began to precipitate at 28° C. The slurrywas held at about 2° C. for 2 hours. The product was isolated vianitration, washed with aqueous ethanol (40%, 3×50 mL), and thenair-dried on the filter for about 1 hour. The title product compound wasobtained as a highly crystalline, light orange powder (70.3 g, 55%yield). No significant impurities were observed by ¹H NMR.

¹H NMR (DMSO-d₆) δ 1.22 (t, 3H), 2.35 (d, 1H), 2.91 (dd, 1H), 4.20 (q,2H), 4.84 (d, 1H), 7.20 (dd, 1H), 7.92 (d, 1H), 8.27 (d, 1H), 10.18 (s,1H).

Step B: Preparation of Ethyl3-chloro-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate(alternatively named ethyl1-(3-chloro-2-pyrdininyl)-3-chloro-2-pyrazoline-5-carboxylate)

To a 2-L four-necked flask equipped with a mechanical stirrer,thermometer, reflux condenser, and nitrogen inlet was chargedacetonitrile (1000 mL), ethyl2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolidinecarboxylate (i.e. theproduct of Step A) (91.0 g, 0.337 mol) and phosphorus oxychloride (35.0mL, 0.375 mol). Upon adding the phosphorus oxychloride, the mixtureself-heated from 22 to 25° C. and a precipitate formed. The light-yellowslurry was heated to reflux at 83° C. over a period of 35 minutes,whereupon the precipitate dissolved. The resulting orange solution washeld at reflux for 45 minutes, whereupon it bad become black-green. Thereflux condenser was replaced with a distillation head, and 650 mL ofsolvent was removed by distillation. A second 2-L four-necked flaskequipped with a mechanical stirrer was charged with sodium bicarbonate(130 g, 1.55 mol) and water (400 mL). The concentrated reaction mixturewas added to the sodium bicarbonate slurry over a period of 15 minutes.The resulting, two-phase mixture was stirred vigorously for 20 minutes,at which time gas evolution had ceased. The mixture was diluted withdichloromethane (250 mL) and then was stirred for 50 minutes. Themixture was treated with Celite® 545 diatomaceous earth filter aid (11g) and then filtered to remove a black, tarry substance that inhibitedphase separation. Since the filtrate was slow to separate into distinctphases, it was diluted with dichloromethane (200 mL) and water (200 mL)and treated with more Celite® 545 (15 g). The mixture was filtered, andthe filtrate was transferred to a separator funnel. The heavier, deepgreen organic layer was separated. A rag layer (50 mL) was refilteredand then added to the organic layer. The organic solution (800 mL) wastreated with magnesium sulfate (30 g) and silica gel (12 g), and theslurry was stirred magnetically for 30 minutes. The slurry was filteredto remove the magnesium sulfate and silica gel, which had become deepblue-green. The filter cake was washed with dichloromethane (100 mL).The filtrate was concentrated on a rotary evaporator. The productconsisted of dark amber oil (92.0 g, 93% yield). The only appreciableimpurities observed by ¹H NMR were 1% starting material and 0.7%acetonitrile.

¹H NMR (DMSO-d₆) δ 1.15 (t, 3H), 3.26 (d, 1H), 3.58 (dd, 1H), 4.11 (q,2H), 5.25 (dd, 1H), 7.00 (dd, 1H), 7.84 (d, 1H), 8.12 (d, 1H).

Step C: Preparation of Ethyl3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylate(alternatively named ethyl1-(3-chloro-2-pyridinyl)-3-chloropyrazole-5-carboxylate)

A 2-L four-necked flask equipped with a mechanical stirrer, thermometer,reflux condenser, and nitrogen inlet was charged with ethyl3-chloro-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate(i.e. the product of Step B) (95% pure, 99.5 g, 0.328 mol), acetonitrile(1000 mL) and sulfuric acid (98%, 35.0 mL, 0.661 mol). The mixtureself-heated from 22 to 35° C. upon adding the sulfuric acid. After beingstirred for several minutes, the mixture was treated with potassiumpersulfonate (140 g, 0.518 mol). The slurry was heated to reflux at 84°C. for 4.5 hours. The resulting orange slurry while still warm (50-65°C.) was filtered to remove a fine, white precipitate. The filter cakewas washed with acetonitrile (50 mL). The filtrate was concentrated toabout 500 mL on a rotary evaporator. A second 2-L four-necked flaskequipped with a mechanical stirrer was charged with water (1250 mL). Theconcentrated reaction mass was added to the water over a period of about5 minutes. The product was isolated via filtration, washed with aqueousacetonitrile (25%, 3×125 mL), washed once with water (100 mL), and thendried overnight in vacuo at room temperature. The product consisted of acrystalline, orange powder (793 g, 82% yield). The only appreciableimparities observed by ¹H NMR were about 1.9% water and 0.6%acetonitrile.

¹H NMR (DMSO-d₆) δ 1.09 (t, 3H), 4.16 (q, 2H), 7.31 (s, 1H), 7.71 (dd,1H), 8.38 (d, 1H), 8.59 (d, 1H).

Step D: Preparation of3-Chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid(alternatively named1-(3-chloro-2-pyridinyl)-3-chloropyrazole-5-carboxylic acid)

A 1-L four-necked flask equipped with a mechanical stirrer, thermometer,and nitrogen inlet was charged with ethyl3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylate (i.e. theproduct of Step C) (97.5% pure, 79.3 g, 0.270 mol), methanol (260 mL),water (140 mL) and sodium hydroxide pellets (13.0 g, 0.325 mol). Uponadding the sodium hydroxide the mixture self-heated from 22 to 35° C.,and the starting material began to dissolve. After being stirred for 45minutes under ambient conditions, all of the starting material haddissolved. The resulting deep orange-brown solution was concentrated toabout 250 mL on a rotary evaporator. The concentrated reaction mixturewas then diluted with water (400 mL). The aqueous solution was extractedwith ether (200 mL). Then the aqueous layer was transferred to a 1-LErlenmeyer flask equipped with a magnetic stirrer. The solution wastreated dropwise with concentrated hydrochloric acid (36.0 g, 0.355 mol)over a period of about 10 minutes. The product was isolated viafiltration, reslurried with water (2×200 mL), cover washed once withwater (100 mL) and then air-dried on the filter for 1.5 hours. Theproduct consisted of a crystalline, light brown powder (58.1 g, 83%yield). About 0.7% ether was the only appreciable impurity observed by¹H NMR.

¹H NMR (DMSO-d₆) δ 7.20 (s, 1H), 7.68 (dd, 1H), 8.25 (d, 1H), 8.56 (d,1H), 13.95 (br s, 1H).

The following Example 13 illustrates an alternative preparation of3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid, whichcan be used to prepare, for example,3-bromo-N-[4-chloro-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamideand3-bromo-N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide,by further steps illustrated in Examples 10 and 11.

Example 13 Preparation of3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid Step A1:Preparation of3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate(alternatively named ethyl1-(3-chloro-2-pyridinyl)-3-bromo-2-pyrazoline-5-carboxylate) usingphospourus oxybromide

A 1-L four-necked flask equipped with a mechanical stirrer, thermometer,reflux condenser, and nitrogen inlet was charged with acetonitrile (400mL), ethyl 2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolidinecarboxylate(i.e. the product of Example 12, Step A) (50.0 g, 0.185 mol) andphosphorus oxybromide (34.0 g, 0.119 mol). The orange slurry was heatedto reflux at 83° C. over a period of 20 minutes. The resulting turbid,orange solution was add at reflux for 75 minutes, at which time a dense,tan, crystalline precipitate had formed. The reflux condenser wasreplaced with a distillation head, and a cloudy, colorless distillate(300 mL) was collected. A second 1-L four-necked flask equipped with amechanical stirrer was charged with sodium bicarbonate (45 g, 0.54 mol)and water (200 mL). The concentrated reaction mixture was added to thesodium bicarbonate slurry over a period of 5 minutes. The resultingtwo-phase mixture was stirred vigorously for 5 minutes, at which timegas evolution had ceased. The mixture was diluted with dichloromethane(200 mL) and then was stirred for 75 minutes. The mixture was treatedwith 5 g of Celite® 545 diatomaceous filter aid and then filtered toremove a brown, tarry substance. The filtrate was transferred to aseparatory funnel. The brown organic layer (400 mL) was separated andthen was treated with magnesium sulfate (15 g) and Darco® G60 activatedcharcoal (2.0 g). The resulting slurry was stirred magnetically for 15minutes and then filtered to remove the magnesium sulfate and charcoal.The green filtrate was treated with silica gel (3 g) and stirred forseveral minutes. The deep blue-green silica gel was removed byfiltration, and the filtrate was concentrated on a rotary evaporator.The product consisted of a light amber oil (58.6 g, 95% yield), whichcrystallized upon standing. The only appreciable impurity observed by ¹HNMR was 0.3% acetonitrile.

¹H NMR (DMSO-d₆) δ 1.15 (t, 3H), 3.29 (dd, 1H), 3.60 (dd, 1H), 4.11 (q,2H), 5.20 (dd, 1H), 6.99 (dd, 1H), 7.84 (d, 1H), 8.12 (d, 1H).

Step A2: Preparation of Ethyl3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylateUsing Phosphorous Pentabromide

A 1-L four-necked flask equipped with a mechanical stirrer, thermometer,reflux condenser, and nitrogen inlet was charged with acetonitrile (330mL), ethyl 2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolidinecarboxylate(i.e. the product of Example 12, Step A) (52.0 g, 0.193 mol), andphosphorus pentabromide (41.0 g, 0.0952 mol). The orange slurry washeated to reflux at 84° C. over a period of 20 minutes. The resultingbrick-red mixture was held at reflux for 90 minutes, at which time adense tan crystalline precipitate had formed. The reflux condenser wasreplaced with a distillation head, and a cloudy, colorless distillate(220 mL) was collected. A second 1-L four-necked flask equipped with amechanical stirrer was charged with sodium bicarbonate (40 g, 0.48 mol)and water (200 mL). The concentrated reaction mixture was added to thesodium bicarbonate slurry over a period of 5 minutes. The resulting,two-phase mixture was stirred vigorously for 10 minutes, at which timegas evolution had ceased. The mixture was diluted with dichloromethame(200 mL) and then was stirred for 10 minutes. The mixture was treatedwith Celite® 545 diatomaceous filter aid (5 g) and then filtered toremove a purple, tarry substance. The filter cake was washed withdichloromethane (50 mL). The filtrate was transferred to a separatoryfunnel. The purple-red organic layer (400 mL) was separated and then wastreated with magnesium sulfate (15 g) and Darco® G60 activated charcoal(2.2 g). The slurry was stirred magnetically for 40 minutes. The slurrywas filtered to remove the magnesium sulfate and charcoal. The filtratewas concentrated on a rotary evaporator. The product consisted of a darkamber oil (61.2 g, 95% yield), which crystallized upon standing. Theonly appreciable impurity observed by ¹H NMR was 0.7% acetonitrile.

¹H NMR (DMSO-d₆) δ 1.15 (t, 3H), 3.29 (dd, 1H), 3.60 (dd, 1H), 4.11 (q,2H), 5.20 (dd, 1H), 6.99 (dd, 1H), 7.84 (d, 1H), 8.12 (d, 1H).

Step B: Preparation of Ethyl3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylate(alternatively named ethyl1-(3-chloro-2-pyridinyl)-3-bromopyrazole-5-carboxylate)

A 1-L four-necked flask equipped with a mechanical stirrer, thermometer,reflux condenser, and nitrogen inlet was charged with ethyl3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate(i.e. the product of Steps A1 and A2) (40.2 g, 0.121 mol), acetonitrile(300 mL) and sulfuric acid (98%, 13.0 mL, 0.245 mol). The mixtureself-heated from 22 to 36° C. upon adding the sulfuric acid. After beingstirred for several minutes, the mixture was treated with potassiumpersulfate (48.0 g, 0.178 mol). The slurry was heated to reflux at 84°C. for 2 hours. The resulting orange slurry while still warm (50-65° C.)was filtered to remove a white precipitate. The filter cake was washedwith acetonitrile (2×50 mL). The filtrate was concentrated to about 200mL on a rotary evaporator. A second 1-L four-necked flask equipped witha mechanical stirrer was charged with water (400 mL). The concentratedreaction mass was added to the water over a period of about 5 minutes.The product was isolated via filtration, washed sequentially withaqueous acetonitrile (20%, 100 mL) and water (75 mL), and was thenair-dried on the filter for 1 hour. The product consisted of acrystalline, orange powder (36.6 g, 90% yield). The only appreciableimpurities observed by ¹H NMR were about 1% of an unknown and 0.5%acetonitrile.

¹H NMR (DMSO-d₆) δ 1.09 (t, 3H), 4.16 (q, 2H), 7.35 (s, 1H), 7.72 (dd,1H), 8.39 (d, 1H), 8.59 (d, 1H).

Step C: Preparation of3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid(alternatively named1-(3-chloro-2-pyridinyl)-3-bromopyrazole-5-carboxylic acid)

A 300-mL four-necked flask equipped with a mechanical stirrer,thermometer, and nitrogen inlet was charged with ethyl3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylate (i.e. theproduct of Step B) (98.5% pure, 25.0 g, 0.0756 mol), methanol (76 mL),water (50 mL), and sodium hydroxide pellets (3.30 g, 0.0825 mol). Uponadding the sodium hydroxide the mixture self-heated from 29 to 34° C.and the starting material began to dissolve. Alter being stirred for 90minutes under ambient conditions, all of the starting material haddissolved. The resulting dark orange solution was concentrated to about90 mL on a rotary evaporator. The concentrated reaction mixture was thendiluted with water (160 mL). The aqueous solution was extracted withether (100 mL). Then the aqueous layer was transferred to a 500-mLErlenmeyer flask equipped with a magnetic stirrer. The solution wastreated dropwise with concentrated hydrochloric acid (8.50 g, 0.0839mol) over a period of about 10 minutes. The product was isolated viafiltration, reslurried with water (2×40 mL), cover washed once withwater (25 mL), and then air-dried on the filter for 2 hours. The productconsisted of a crystalline, tan powder (20.9 g, 91% yield). The onlyappreciable impurities observed by ¹H NMR were about 0.8% of an unknownand 0.7% ether.

¹H NMR (DMSO-d₆) δ 7.25 (s, 1H), 13.95 (br s, 1H), 8.56 (d, 1H), 8.25(d, 1H), 7.68 (dd, 1H).

The following Example 14 illustrates an alternative preparation of ethyl3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate,which can be used to prepare, for example, ethyl3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylate (i.e. productof Example 13, Step B).

Example 14 Preparation of Ethyl3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylatefrom ethyl3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylateusing hydrogen bromide

Hydrogen bromide was passed through a solution of ethyl3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate(i.e. product of Example 12, Step B) (8.45 g, 29.3 mmol) indibromomethane (85 mL). After 90 minutes the gas flow was terminated,and the reaction mixture was washed with aqueous sodium bicarbonatesolution (100 mL). The organic phase was dried and evaporated underreduced pressure to give the title product as an oil (9.7 g, 99% yield),which crystallized on standing.

¹H NMR (CDCl₃) δ 1.19 (t, 3H), 3.24 (½ of AB in ABX pattern, J=9.3, 17.3Hz, 1H), 3.44 (½ of AB in ABX pattern, J=11.7, 17.3 Hz, 1H), 4.18 (q,2H), 5.25 (X of ABX, 1H, J=9.3, 11.9 Hz), 6.85 (dd, J=4.7, 7.7 Hz, 1H),7.65 (dd, J=1.6, 7.8 Hz, 1H), 8.07 (dd, J=1.6, 4.8 Hz, 1H).

The following Example 15 illustrates the preparation of ethyl3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[[(4-methylphenyl)sulfonyl]oxy]-1H-pyrazole-5-carboxylate,which can be used to prepare ethyl3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylateby procedures similar to that described in Example 14.

Example 15 Preparation of ethyl1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[[(4-methylphenyl)sulfonyl]oxy]-1H-pyrazole-5-carboxylate

Triethylamine (3.75 g, 37.1 mmol) was added dropwise to a mixture ofethyl 2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolidinecarboxylate (i.e. theproduct of Example 12, Step A) (10.0 g, 37.1 mmol) and p-toluenesulfonylchloride (7.07 g, 37.1 mmol) in dichloromethane (100 mL) at 0° C.Further portions of p-toluenesulfonyl chloride (0.35 g, 1.83 mmol) andtriethylamine (0.19 g, 1.88 mmol) were added. The reaction mixture wasthen allowed to warm to room temperature and was stirred overnight. Themixture was then diluted with dichloromethane (200 mL) and washed withwater (3×70 mL). The organic phase was dried and evaporated to leave thetitle product as an oil (13.7 g, 87% yield), which slowly formedcrystals. Product recrystallized from ethyl, acetate/hexanes melted at99.5-100° C.

IR (nujol) ν 740, 1638, 1576, 1446, 1343, 1296, 1228, 1191, 1178, 1084,1027, 948, 969, 868, 845 cm⁻¹.

¹H NMR (CDCl₃) δ 1.19 (t, 3H), 2.45 (s, 3H), 3.12 (½ of AB in ABXpattern, J=17.3, 9 Hz, 1H), 3.33 (½ of AB in ABX pattern, J=17.5, 11.8Hz, 1H), 4.16 (q, 2H), 5.72 (X of ABX, J=9, 11.8 Hz, 1H), 6.79 (dd,J=4.6, 7.7 Hz, 1H), 7.36 (d, J=8.4 Hz, 2H), 7.56 (dd, J=1.6, 7.8 Hz,1H), 7.95 (d, J=8.4 Hz, 2H), 8.01 (dd, J=1.4, 4.6 Hz, 1H).

Example 16 Preparation ofN-[4-Chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-3-(2,2,2-trifluoroethoxy)-1H-pyrazole-5-carboxamideStep A: Preparation of Ethyl1-(3-chloro-2-pyridinyl)-2,3-dihydro-3-oxo-1H-pyrazole-5-carboxylate

To a suspension of ethyl2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolinecarboxylate (i.e. product ofExample 12, Step A) (27 g, 100 mmol) stirred in dry acetonitrile (200mL) was added sulfuric acid (20 g, 200 mmol) in one portion. Thereaction mixture thinned to form a pale green, nearly clear solutionbefore thickening again to form a pale yellow suspension. Potassiumpersulfate (33 g, 120 mmol) was added in one portion, and then thereaction mixture was heated at gentle reflux for 3.5 hours. Aftercooling using an ice bath, a precipitate of white solid was removed byfiltration and discarded. The filtrate was diluted with water (400 mL)and then extracted three times with ethyl ether (700 mL total).Concentration of the combined ether extracts to a reduced volume (75 mL)caused precipitation of an off-white solid (3.75 g), which was collectedby filtration. The ether mother liquor was further concentrated to yielda second crop of an off-white precipitate (4.2 g), which was alsocollected by filtration. An off-white solid also precipitated from theaqueous phase; this solid (4.5 g) was collected by filtration to providea combined total of 12.45 g of the title compound.

¹H NMR (DMSO-d₆) δ 1.06 (t, 3H), 4.11 (q, 2H), 6.34 (s, 1H), 7.6 (t,1H), 8.19 (d, 1H), 8.5 (d, 1H), 10.6 (s, 1H).

Step B: Preparation of Ethyl1-(3-chloro-2-pyridinyl)-3-(2,2,2-trifluoroethoxy)-1H-pyrazole-5-carboxylate

To a suspension of ethyl1-(3-chloro-2-pyridinyl)-2,3-dihydro-3-oxo-1H-pyrazole-5-carboxylate(i.e. product of Step A) (0.1 g, 3 mmol) stirred is dry acetonitrile (15mL) at −5° C. was added potassium carbonate (0.85 g, 6.15 mmol). Thesuspension was stirred for 15 minutes at 20° C. The stirred suspensionwas then cooled to 5° C. and 2,2,2-trifluoro-ethyltrifluoromethanesulfonate (0.8 g, 3.45 mmol) was added dropwise. Thereaction mixture was warmed to room temperature and then heated toreflux, at which time thin layer chromatography showed the reaction tobe complete. Water (25 mL) was added to the reaction mixture, which wasthen extracted with ethyl ether. The ether extract was dried overmagnesium sulfate and concentrated to yield the title product compound(1.05 g) as a pale yellow oil.

¹H NMR (CDCl₃) δ 1.21 (t, 3H), 4.20 (q, 2H), 4.63 (q, 2H), 6.53 (s, 1H),7.4 (t, 1H), 7.9 (d, 1H), 8.5 (d, 1H).

Step C: Preparation of1-(3-chloro-2-pyridinyl)-3-(2,2,2-trifluoroethoxy)-1H-pyrazole-5-carboxylicacid

To a stirred solution of ethyl1-(3-chloro-2-pyridinyl)-3-(2,2,2-trifluoroethoxy)-1H-pyrazole-5-carboxylate(i.e. product of Step B) (0.92 g, 2.1 mmol) in methanol. (15 mL) wasadded water (5 mL), which caused the reaction mixture to become cloudy.An aqueous solution of sodium hydroxide (50%, 1.5 g, 19.2 mmol) wasadded dropwise, and the reaction mixture was stirred at room temperaturefor 30 minutes, during which time the reaction mixture became againclear. Water (20 mL) was added and the reaction mixture was extractedwith ethyl ether, which was discarded. The aqueous phase was acidifiedto pH 2 using concentrated hydrochloric acid and then extracted withethyl acetate (50 mL). The ethyl acetate extract, which was washed withwater (20 mL) and brine (20 mL), dried over magnesium sulfate andconcentrated to give the title compound, isolated as a white solid (0.8g)

¹H NMR (DMSO-d₆) δ 4.9 (q, 2H), 6.75 (s, 1H), 7.6 (t, 1H), 8.2 (d, 1H),8.55 (d, 1H), 13.7 (bs, 1H).

Step D: Preparation of 6-Chloro-8-methyl-2H-3,1-bezoxazine-2,4(1H)-dione

To a suspension of 2-amino-3-methyl-5-chlorobenzoic acid (i.e. productof Example 6, Step A) (97 g, 520 mmol) stored in dry dioxane (750 mL) atroom temperature, trichloromethyl chloroformate (53 g, 320 mmol) wasadded dropwise. The reaction mixture exothermically warmed slowly to 42°C., and the solid almost completely dissolved before a thick suspensionformed again. After the suspension was stirred at ambient temperaturefor 2.5 hours, the title compound was isolated by filtration, washedwith ethyl ether, and dried to yield the title product compound,obtained as a white solid (98 g).

¹H NMR (DMSO-d₆) δ 2.3 (s, 3H), 7.70 (s, 1H), 7.75 (s, 1H), 11.2 (s,1H).

Step E: Preparation of6-Chloro-2-[1-(3-chloro-2-pyridinyl)-3-(2,2,2-trifluoromethoxy)-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazin-4-one

To a suspension of1-(3-chloro-2-pyridinyl)-3-(2,2,2-trifluoroethoxy)-1H-pyrazole-5-carboxylateacid (i.e. product of Step C) (7.9 g, 24 mmol) stirred indichloromethane (100 mL) was added N,N-dimethylformamide (4 drops).Oxalyl chloride (4.45 g, 35 mmol) was added dropwise over a period of 45minutes. The resulting solution was stirred at room temperature for 4hours and then concentrated under vacuum. The isolated acid chloride wasdissolved in dry acetonitrile (10 mL) and added to a suspension of6-chloro-8-methyl-2H-3,1-benzoxazine-2,4(1H)-dione (i.e. product of StepD) (4.9 g, 23 mmol) stirred in dry acetonitrile (14 mL). Pyridine (10mL) was added, and the solution heated at reflux 6 hours. After coolingusing an ice bath, a precipitate of white solid (9.15 g) was collected.The ¹H NMR spectrum of the collected precipitate showed peaks consistentwith the title compound and residual6-chloro-8-methyl-2H-3,1-benzoxazine-2,4-(1H)-dione starting material. Asmall portion of the collected precipitate was recrystallized fromacetonitrile to yield the pure title product melting at 178-180° C.

¹H NMR (DMSO-d₆) δ 1.72 (s, 3H), 4.96 (q, 2H) 7.04 (s, 1H), 7.7 (t, 1H),7.75 (s, 1H), 7.9 (s, 1H), 8.3 (d, 1H), 8.6 (d, 1H).

Step F: Preparation ofN-[4-chloro-2-methyl-6-[methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-3-(2,2,2-trifluoroethoxy)-1H-pyrazole-5-carboxamide

To a suspension of the6-Chloro-2-[1-(3-chloro-2-pyridinyl)-3-(2,2,2-trifluoromethoxy)-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazin-4-one(i.e. precipitate product of Step E) (3.53 g, 7.5 mmol) intetrahydrofuran (15 mL), methylamine (2.0 M solution in THF, 11 mL, 22mmol) was added dropwise, and the resulting solution was stirred at roomtemperature for 45 minutes. Thin layer chromatography then showed thereaction to be complete. Ethyl ether (100 mL) was added, and thereaction mixture was stirred for 2 hours while a precipitate formed. Theprecipitate was collected by filtration and then recrystallized fromacetonitrile to yield a white solid (0.82 g). A second crop of whitesolid (0.35 g) precipitated from the acetonitrile mother liquor and wascollected by filtration. The initial ether/tetrahydrofuran mother liquorwas concentrated to dryness, and the residual solid was recrystallizedfrom acetonitrile to yield a third crop of white solid (0.95 g). Thethree crops were combined, totaling 2.12 g (after drying) of the titlecompound, a compound of the present invention, isolated as a whitesolid, melting at 195-197° C.

¹H NMR (CDCl₃) δ 2.18 (s, 3H), 2.92 (d, 3H), 4.66 (q, 2H), 6.15 (q, 1H),6.6 (s, 1H), 7.2 (s, 1H), 7.25 (s, 1H), 73.5 (t, 1H), 73 (d, 1H), 8.45(d, 1H), 10.0 (s, 1H).

The following Example 17 illustrates an alternative preparation1-(3-chloro-2-pyridinyl)-3-1H-pyrazole-5-carboxylic acid, which can beused to prepare, for example,1-(3-chloro-2-pyrdinyl)-N-[2-methyl-6-[[(1-methylethyl)amino]carbonyl]-phenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide,by further steps illustrated in Examples 4.

Example 17 Preparation1-(3-chloro-2-pyridinyl)-3(trifluoroethoxy)-1H-pyrazole-5-carboxylicacid Step A: Preparation of3-chloro-2(1H)-pyridinone-(2,2,2-trifluoro-1-methylethyldene)hydrazone

1,1,1-Trifluoroacetone (7.80 g, 69.6 mmol) was added to3-chloro-2-(1H)-pyridinone hydrazone (alternatively named(3-chloro-pyridin-2-yl)-hydrazine) (10 g, 69.7 mmol) at 20-25° C. Afterthe addition was complete, the mixture was stirred for about 10 minutes.The solvent was removed under reduced pressure and the mixturepartitioned between ethyl acetate (100 mL) and saturated aqueous sodiumcarbonate solution (100 mL). The organic layer was dried and evaporated.Chromatography on silica gel (eluted with ethyl acetate) gave theproduct as an off-white solid (11 g, 66% yield), m.p. 64-64.5° C. (aftercrystallization from ethyl acetate/hexanes).

IR (nujol) ν 1629, 1590, 1518, 1403, 1365, 1309, 1240, 1196, 1158, 1100,1032, 992, 800 cm⁻¹.

¹H NMR (DMSO-d₆) δ 2.12 (s, 3H), 6.91-6.86 (m, 1H), 7.64-7.61 (m, 1H),8.33-8.32 (m, 2H), MS m/z 237 (M⁺).

Step B: Preparation of ethyl hydrogen ethanedioate(3-chloro-2-pyridinyl)(2,2,2-trifluoro-1-methylethylidene)hydrazide(alternatively named ethyl hydrogen ethanedioate(3-chloro-2-pyridinyl)(2,2,2-trifluoro-1-methylethylidene)hydrazine)

Triethylamine (20.81 g, 03.06 mol) was added to3-chloro-2(1H)-pyridinone (2,2,2-trifluoro-1-methylethylidene)hydrazone(i.e. the product of Step A) (32.63 g, 0.137 mol) in dichloromethane (68mL) at 0° C. Ethyl chlorooxoacetate (18.75 g, 0.137 mol) indichloromethane (69 mL) was added dropwise to the mixture at 0° C. Themixture was allowed to warm to 25° C. over about 2 hours. The mixturewas cooled to 0° C. and a further portion of ethyl chlorooxoacetate(3.75 g, 27.47 mmol) in dichloromethane (14 mL) was added dropwise.After about an additional 1 hour, the mixture was dilated withdichloromethane (about 450 mL), and the mixture was washed with water(2×150 mL). The organic layer was dried and evaporated. Chromatographyon silica gel (eluted with 1:1 ethyl acetate-hexanes) gave the productas a solid (42.06 g, 90% yield), m.p. 73.0-73.5° C. (aftercrystallization from ethyl acetate/hexanes).

IR (nujol) ν 1751, 1720, 1664, 1572, 1417, 1361, 1330, 1202, 1214, 1184,1137, 1110, 1004, 1043, 1013, 942, 807, 836 cm⁻¹.

¹H NMR (DMSO-d₆, 115° C.) 1.19 (t, 3H), 1.72 (br s, 3H), 4.25 (q, 2H),7.65 (dd, J=8.3, 4.7 Hz, 1H), 8.20 (dd, J=7.6, 1.5 Hz, 1H), 8.55 (d,J=3.6 Hz, 1H).

MS m/z 337 (M⁺).

Step C: Preparation of ethyl1-(3-chloro-2-pyridinyl)-4,5-dihydro-5-hydroxy-3-(trifluormethyl)-1H-pyrazole-5-carboxylate

Ethyl hydrogen ethanedioate(3-chloro-2-pyridinyl)(2,2,2-trifluoro-1-methyl-ethylidene)hydrazide(i.e. the product of Step B) (5 g, 14.8 mmol) in dimethyl sulfoxide (25mL) was added to tetrabutylammonium fluoride hydrate (10 g) in dimethylsulfoxide (25 mL) over 8 hours. When the addition was complete, themixture was poured into acetic acid (3.25 g) in water (25 mL). Afterstirring at 25° C. overnight, the mixture was then extracted withtoluene (4×25 mL), and the combined toluene extracts were washed withwater (50 mL), dried and evaporated to give a solid. Chromatography onsilica gel (eluted with 1:2 ethyl acetate-hexanes) gave the product as asolid (2.91 g, 50% yield, containing about 5% of3-chloro-2(1H)-pyridinone(2,2,2-trifluoro-1-methylethylidene)hydrazone), m.p. 78-78.5° C. (afterrecrystallization from ethyl acetate/hexanes).

IR (nujol) ν 3403, 1726, 1618, 1582, 1407, 1320, 1293, 1260, 1217, 1187,1150, 1122, 1100, 1067, 1013, 873, 829 cm⁻¹.

¹H NMR (CDCl₃) δ 1.19 (s, 3H), 3.20 (½ of ABZ pattern, J=18 Hz, 1H),3.42 (½ of ABZ pattern, J=18 Hz, 1H), 4.24 (q, 2H), 6.94 (dd, J=7.9, 4.9Hz, 1H), 7.74 (dd, J=7.7, 1.5 Hz, 1H), 8.03 (dd, J=4.7, 1.5 Hz, 1H).

MS m/z 319 (M⁺),

Step D: Preparation of ethyl1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylate

Sulfuric acid (concentrated, 2 drops) was added to ethyl1-(3-chloro-2-pyridinyl-4,5-dihydro-5-hydroxy-3-(trifluoromethyl)-1H-pyrazole-5-carboxylate(i.e. the product of Step C) (1 g, 2.96 mmol) in acetic acid (10 mL) andthe mixture was warmed to 65° C. for about 1 hour. The mixture wasallowed to cool to 25° C. and most of the acetic acid was removed underreduced pressure. The mixture was partitioned between saturated aqueoussodium carbonate solution (100 mL) and ethyl acetate (100 mL). Theaqueous layer was further extracted with ethyl acetate (100 mL). Thecombined organic extracts were dried and evaporated to give the productas an oil (0.66 g, 77% yield).

IR (neat) ν 3147, 2986, 1734, 1577, 1547, 1466, 1420, 1367, 1277, 1236,1135, 1082, 1031, 973, 842, 802 cm⁻¹.

¹H NMR (CDCl₃) δ 1.23 (t, 3H), 4.25 (q, 2H), 7.21 (s, 1H), 7.48 (dd,J=8.1, 4.7 Hz, 1H), 7.94 (dd, J=6.6, 2 Hz, 1H), 8.53 (dd, J=4.7, 1.5 Hz,1H).

Step E: Preparation of1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylicacid

Potassium hydroxide (0.5 g, 85%, 2.28 mmol) in water (1 mL) was added toethyl1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylate(i.e. the product of Step D) (0.66 g, 2.07 mmol) in ethanol (3 mL).After about 30 minutes, the solvent was removed under reduced pressure,and the mixture was dissolved in water (40 mL). The solution was washedwith ethyl acetate (20 mL). The aqueous layer was acidified withconcentrated hydrochloric acid and was extracted with ethyl acetate(3×20 mL). The combined extracts were dried and evaporated to give theproduct as a solid 0.53 g, 93% yield), m.p. 178-179° C. (aftercrystallization from hexanes-ethyl acetate).

IR (nujol) ν 1711, 1586, 1565, 1550, 1440, 1425, 1292, 1247, 1219, 1170,1135, 1087, 1059, 1031, 972, 843, 816 cm⁻¹.

¹H NMR (DMSO-d₆) δ 7.61 (s, 1H), 7.77 (m, 1H), 8.30 (d, 1H), 8.60 (a,1H).

Examples 18 and 19 illustrate alternatives to reaction conditionsdescribed in Example 10, Step E and Example 8, Step E, respectively.

Example 18 Preparation of2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazin-4-one

Methanesulfonyl chloride (1.0 mL, 1.5 g, 13 mmol) was dissolved inacetonitrile (10 mL), and the mixture was cooled to −5° C. A solution of3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (i.e. thepyrazolecarboxylic acid product of Example 10, Step D) (3.02 g, 10 mmol)and pyridine (1.4 mL, 1.4 g, 17 mmol) in acetonitrile (10 mL) was addeddropwise over 5 minutes at −5 to 0° C. A slurry formed during theaddition. The mixture was stirred 5 minutes at this temperature, andthen a mixture of 2-amino-3-methyl-5-chlorobenzoic acid (i.e. theproduct of Example 6 Step A) (1.86 g, 10 mmol) and pyridine (2.8 mL, 2.7g, 35 mmol) in acetonitrile (10 mL) was added, rising with moreacetonitrile (5 mL). The mixture was stirred 15 minutes at −5 to 0° C.,and then methanesulfonyl chloride (1.0 mL, 1.5 mL, 13 mmol) inacetonitrile (5 mL) was added, dropwise over 5 minutes at a temperatureof −5 to 0° C. The reaction mixture was stirred 15 minutes more at thistemperature, then allowed to warm slowly to room temperature, andstirred 4 h. Water (20 mL) was added dropwise, and the mixture wasstirred 15 minutes. Then the mixture was filtered, and the solids werewashed with 2:1 acetonitrile-water (3×3 mL), to with acetonitrile (2×3mL), and dried under nitrogen to afford the title product as a lightyellow powder, 4.07 g (90.2% crude yield), melting at 203-205° C. HPLCof the product using a Zorbax® RX-C8 chromatography column (4.6 mm×25cm, eluent 25-95% acetonitrile/pH 3 water) showed a major peakcorresponding to the title compound and having 95.7% of totalchromatogram peak area.

¹H NMR (DMSO-d₆) δ 1.72 (s, 3H) 7.52 (s, 1H), 7.72-7.78 (m, 2H), 7.88(m, 1H), 8.37 (dd, 1H), 8.52 (dd, 1H).

Example 19 Preparation of6-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-one

Methanesulfonyl chloride (1.0 mL, 1.5 g, 13 mmol) was dissolved inacetonitrile (10 mL), and the mixture was cooled to −5° C. A solution of3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (i.e.the carboxylic acid product of Example 8, Step D) (2.58 g, 10 mmol) andpyridine (1.4 mL, 1.4 g, 17 mmol) in acetonitrile (10 mL) was addeddropwise over 5 minutes at −5 to 0° C. A slurry formed during theaddition. The mixture was stirred 5 minutes at this temperature, andthen 2-amino-3-methyl-5-chlorobenzoic acid (i.e. the product fromExample 6, Step A) (1.86 g, 10 mmol) was added all at once. Then asolution of pyridine (2.8 mL, 2.7 g, 35 mmol) in acetonitrile (10 mL)was added dropwise in 5 min at −5 to 0° C. The mixture was stirred 15minutes at −5 to 0° C., and then methanesulfonyl chloride (1.0 mL, 1.5mL, 13 mmol) in acetonitrile (5 mL) was added dropwise in 5 min at −5 to0° C. The reaction mixture was stirred 15 minutes at this temperature,then allowed to warm slowly to room temperature, and stirred 4 h. Water(15 mL) was added dropwise and the mixture was stirred 15 minutes. Thenthe mixture was filtered and the solids were washed with 2:1acetonitrile-water (3×3 mL), then with acetonitrile (2×3 mL), and driedunder nitrogen to afford the title product as a pale yellow powder, 3.83g (94.0% crude yield), melting at 199-201° C. HPLC of the product usinga Zorbax® RX-C8 chromatography column (4.6 mm×25 cm, eluent 25-95%acetonitrile/pH 3 water) showed a major peak corresponding to the titlecompound and having 97.8% of total chromatogram peak area.

¹H NMR (DMSO-d₆) δ 1.72 (s, 3H), 7.48 (s, 1H), 7.74-7.30 (m, 2H), 7.87(m, 1H), 8.37 (dd, 1H), 8.62 (dd, 1H).

By the procedures described herein together with methods known in theart, the following compounds of Table 1 can be prepared. The followingabbreviations are used in the Tables which follow: t means tertiary, smeans secondary, n means normal, i means iso, Me means methyl, Et meansethyl, Pr means propyl, i-Pr means isopropyl, and Bu means butyl.

TABLE 1

R³ R⁴ Q X Y Z i-Pr Me NMe N CH CCF₃ i-Pr Me NMe N CH CC₂F₅ i-Pr Cl NMe NCH CCF₃ i-Pr Cl NMe N CH CC₂F₅ i-Pr Br NMe N CH CCF₃ i-Pr Br NMe N CHCC₂F₅ i-Pr I NMe N CH CCF₃ i-Pr I NMe N CH CC₂F₅ i-Pr F NMe N CH CCF₃i-Pr F NMe N CH CC₂F₅ i-Pr H NMe N CH CCF₃ i-Pr H NMe N CH CC₂F₃ i-Pr EtNMe N CH CCF₃ i-Pr Et NMe N CH CC₂F₅ i-Pr Me NEt N CH CCF₃ t-Bu Me NMe NCH CCF₃ i-Pr Cl NEt N CH CCF₃ t-Bu Cl NMe N CH CCF₃ i-Pr Br NEt N CHCCF₃ t-Bu Br NMe N CH CCF₃ i-Pr I NEt N CH CCF₃ t-Bu I NMe N CH CCF₃i-Pr F NEt N CH CCF₃ t-Bu F NMe N CH CCF₃ i-Pr H NEt N CH CCF₃ t-Bu HNMe N CH CCF₃ i-Pr Et NEt N CH CCF₃ t-Bu Et NMe N CH CCF₃

TABLE 2

W X Y Z R³ R⁴ R⁶ R⁹ CH CH CH CH i-Pr Me CF₃ Me CH CH CH CH t-Bu Me CF₃Me CH CH CH CH i-Pr Cl CF₃ Me CH CH CH CH t-Bu Cl CF₃ Me CH CH CH CHi-Pr Br CF₃ Me CH CH CH CH t-Bu Br CF₃ Me CH CH CH CH i-Pr Me Cl Me CHCH CH CH t-Bu Me Cl Me CH CH CH CH i-Pr Cl Cl Me CH CH CH CH t-Bu Cl ClMe CH CH CH CH i-Pr Br Cl Me CH CH CH CH t-Bu Br Cl Me CH CH CH CH i-PrMe Br Me CH CH CH CH t-Bu Me Br Me CH CH CH CH i-Pr Cl Br Me CH CH CH CHt-Bu Cl Br Me CH CH CH CH i-Pr Br Br Me CH CH CH CH t-Bu Br Br Me CH CHCH CH i-Pr Me CN Me CH CH CH CH t-Bu Me CN Me CH CH CH CH i-Pr Cl CN MeCH CH CH CH t-Bu Cl CN Me CH CH CH CH i-Pr Br CN Me CH CH CH CH t-Bu BrCN Me CH CH CH CH i-Pr Me CF₃ F CH CH CH CH t-Bu Me CF₃ F CH CH CH CHi-Pr Cl CF₃ F CH CH CH CH t-Bu Cl CF₃ F CH CH CH CH i-Pr Br CF₃ F CH CHCH CH t-Bu Br CF₃ F CH CH CH CH i-Pr Me Cl F CH CH CH CH t-Bu Me Cl F CHCH CH CH i-Pr Cl Cl F CH CH CH CH t-Bu Cl Cl F CH CH CH CH i-Pr Br Cl FCH CH CH CH t-Bu Br Cl F CH CH CH CH i-Pr Me Br F CH CH CH CH t-Bu Me BrF CH CH CH CH i-Pr Cl Br F CH CH CH CH t-Bu Cl Br F CH CH CH CH i-Pr BrBr F CH CH CH CH t-Bu Br Br F CH CH CH CH i-Pr Me CN F CH CH CH CH t-BuMe CN F CH CH CH CH i-Pr Cl CN F CH CH CH CH t-Bu Cl CN F CH CH CH CHi-Pr Br CN F CH CH CH CH t-Bu Br CN F CH CH CH CH i-Pr Me CF₃ Cl CH CHCH CH t-Bu Me CF₃ Cl CH CH CH CH i-Pr Cl CF₃ Cl CH CH CH CH t-Bu Cl CF₃Cl CH CH CH CH i-Pr Br CF₃ Cl CH CH CH CH t-Bu Br CF₃ Cl CH CH CH CHi-Pr Me Cl Cl CH CH CH CH t-Bu Me Cl Cl CH CH CH CH i-Pr Cl Cl Cl CH CHCH CH t-Bu Cl Cl Cl CH CH CH CH i-Pr Br Cl Cl CH CH CH CH t-Bu Br Cl ClCH CH CH CH i-Pr Me Br Cl CH CH CH CH t-Bu Me Br Cl CH CH CH CH i-Pr ClBr Cl CH CH CH CH t-Bu Cl Br Cl CH CH CH CH i-Pr Br Br Cl CH CH CH CHt-Bu Br Br Cl CH CH CH CH i-Pr Me CN Cl CH CH CH CH t-Bu Me CN Cl CH CHCH CH i-Pr Cl CN Cl CH CH CH CH t-Bu Cl CN Cl CH CH CH CH i-Pr Br CN ClCH CH CH CH t-Bu Br CN Cl CH CH CH CH i-Pr Me CF₃ Br CH CH CH CH t-Bu MeCF₃ Br CH CH CH CH i-Pr Cl CF₃ Br CH CH CH CH t-Bu Cl CF₃ Br CH CH CH CHi-Pr Br CF₃ Br CH CH CH 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i-Pr Me Br F CH CH CH N t-Bu Me Br FCH CH CH N i-Pr Cl Br F CH CH CH N t-Bu Cl Br F CH CH CH N i-Pr Br Br FCH CH CH N t-Bu Br Br F CH CH CH N i-Pr Me CN F CH CH CH N t-Bu Me CN FCH CH CH N i-Pr Cl CN F CH CH CH N t-Bu Cl CN F CH CH CH N i-Pr Br CN FCH CH CH N t-Bu Br CN F CH CH CH N i-Pr Me CF₃ Cl CH CH CH N t-Bu Me CF₃Cl CH CH CH N i-Pr Cl CF₃ Cl CH CH CH N t-Bu Cl CF₃ Cl CH CH CH N i-PrBr CF₃ Cl CH CH CH N t-Bu Br CF₃ Cl CH CH CH N i-Pr Me Cl Cl CH CH CH Nt-Bu Me Cl Cl CH CH CH N i-Pr Cl Cl Cl CH CH CH N t-Bu Cl Cl Cl CH CH CHN i-Pr Br Cl Cl CH CH CH N t-Bu Br Cl Cl CH CH CH N i-Pr Me Br Cl CH CHCH N t-Bu Me Br Cl CH CH CH N i-Pr Cl Br Cl CH CH CH N t-Bu Cl Br Cl CHCH CH N i-Pr Br Br Cl CH CH CH N t-Bu Br Br Cl CH CH CH N i-Pr Me CN ClCH CH CH N t-Bu Me CN Cl CH CH CH N i-Pr Cl CN Cl CH CH CH N t-Bu Cl CNCl CH CH CH N i-Pr Br CN Cl CH CH CH N t-Bu Br CN Cl CH CH CH N i-Pr MeCF₃ Br CH CH CH N t-Bu Me CF₃ Br CH CH CH N i-Pr Cl CF₃ Br CH CH CH Nt-Bu Cl CF₃ Br CH CH CH N i-Pr Br CF₃ Br CH CH CH N t-Bu Br CF₃ Br CH CHCH N i-Pr Me Cl Br CH CH CH N t-Bu Me Cl Br CH CH CH N i-Pr Cl Cl Br CHCH CH N t-Bu Cl Cl Br CH CH CH N i-Pr Br Cl Br CH CH CH N t-Bu Br Cl BrCH CH CH N i-Pr Me Br Br CH CH CH N t-Bu Me Br Br CH CH CH N i-Pr Cl BrBr CH CH CH N t-Bu Cl Br Br CH CH CH N i-Pr Br Br Br CH CH CH N t-Bu BrBr Br CH CH CH N i-Pr Me CN Br CH CH CH N t-Bu Me CN Br CH CH CH N i-PrCl CN Br CH CH CH N t-Bu Cl CN Br CH CH CH N i-Pr Br CN Br CH CH CH Nt-Bu Br CN Br CH CH CH N i-Pr Me CF₃ CN CH CH CH N t-Bu Me CF₃ CN CH CHCH N i-Pr Cl CF₃ CN CH CH CH N t-Bu Cl CF₃ CN CH CH CH N i-Pr Br CF₃ CNCH CH CH N t-Bu Br CF₃ CN CH CH CH N i-Pr Me Cl CN CH CH CH N t-Bu Me ClCN CH CH CH N i-Pr Cl Cl CN CH CH CH N t-Bu Cl Cl CN CH CH CH N i-Pr BrCl CN CH CH CH N t-Bu Br Cl CN CH CH CH N i-Pr Me Br CN CH CH CH N t-BuMe Br CN CH CH CH N i-Pr Cl Br CN CH CH CH N t-Bu Cl Br CN CH CH CH Ni-Pr Br Br CN CH CH CH N t-Bu Br Br CN CH CH CH N i-Pr Me CN CN CH CH CHN t-Bu Me CN CN CH CH CH N i-Pr Cl CN CN CH CH CH N t-Bu Cl CN CN CH CHCH N i-Pr Br CN CN CH CH CH N t-Bu Br CN CN CH CH CH CH Me Me CF₃ F CHCH CH CH Et Me CF₃ F CH CH CH CH CH(CH₃)CH₂OCH₃ Me CF₃ F CH CH CH CHCH(CH₃)CH₂SCH₃ Me CF₃ F CH CH CH CH propargyl Me CF₃ F CH CH CH CH Me MeCF₃ Cl CH CH CH CH Et Me CF₃ Cl CH CH CH CH CH(CH₃)CH₂OCH₃ Me CF₃ Cl CHCH CH CH CH(CH₃)CH₂SCH₃ Me CF₃ Cl CH CH CH CH propargyl Me CF₃ Cl CH CHCH CH Me Me Br F CH CH CH CH Et Me Br F CH CH CH CH CH(CH₃)CH₂OCH₃ Me BrF CH CH CH CH CH(CH₃)CH₂SCH₃ Me Br F CH CH CH CH propargyl Me Br F CH CHCH CH Me Me Br Cl CH CH CH CH Et Me Br Cl CH CH CH CH CH(CH₃)CH₂OCH₃ MeBr Cl CH CH CH CH CH(CH₃)CH₂SCH₃ Me Br Cl CH CH CH CH propargyl Me Br ClCH CH CH CH Me Cl CF₃ F CH CH CH CH Et Cl CF₃ F CH CH CH CHCH(CH₃)CH₂OCH₃ Cl CF₃ F CH CH CH CH CH(CH₃)CH₂SCH₃ Cl CF₃ F CH CH CH CHpropargyl Cl CF₃ F CH CH CH CH Me Cl CF₃ Cl CH CH CH CH Et Cl CF₃ Cl CHCH CH CH CH(CH₃)CH₂OCH₃ Cl CF₃ Cl CH CH CH CH CH(CH₃)CH₂SCH₃ Cl CF₃ ClCH CH CH CH propargyl Cl CF₃ Cl CH CH CH CH Me Cl Br F CH CH CH CH Et ClBr F CH CH CH CH CH(CH₃)CH₂OCH₃ Cl Br F CH CH CH CH CH(CH₃)CH₂SCH₃ Cl BrF CH CH CH CH propargyl Cl Br F CH CH CH CH Me Cl Br Cl CH CH CH CH EtCl Br Cl CH CH CH CH CH(CH₃)CH₂OCH₃ Cl Br Cl CH CH CH CH CH(CH₃)CH₂SCH₃Cl Br Cl CH CH CH CH propargyl Cl Br Cl CH CH CH N Me Me CF₃ F CH CH CHN Et Me CF₃ F CH CH CH N CH(CH₃)CH₂OCH₃ Me CF₃ F CH CH CH NCH(CH₃)CH₂SCH₃ Me CF₃ F CH CH CH N propargyl Me CF₃ F CH CH CH N Me MeCF₃ F CH CH CH N Et ME CF₃ Cl CH CH CH N CH(CH₃)CH₂OCH₃ Me CF₃ Cl CH CHCH N CH(CH₃)CH₂SCH₃ Me CF₃ Cl CH CH CH N propargyl Me CF₃ Cl CH CH CH NMe Me Br F CH CH CH N Et Me Br F CH CH CH N CH(CH₃)CH₂OCH₃ Me Br F CH CHCH N CH(CH₃)CH₂SCH₃ Me Br F CH CH CH N propargyl Me Br F CH CH CH N MeMe Br Cl CH CH CH N Et Me Br Cl CH CH CH N CH(CH₃)CH₂OCH₃ Me Br Cl CH CHCH N CH(CH₃)CH₂SCH₃ Me Br Cl CH CH CH N propargyl Me Br Cl CH CH CH N MeCl CF₃ F CH CH CH N Et Cl CF₃ F CH CH CH N CH(CH₃)CH₂OCH₃ Cl CF₃ F CH CHCH N CH(CH₃)CH₂SCH₃ Cl CF₃ F CH CH CH N propargyl Cl CF₃ F CH CH CH N MeCl CF₃ Cl CH CH CH N Et Cl CF₃ Cl CH CH CH N CH(CH₃)CH₂OCH₃ Cl CF₃ Cl CHCH CH N CH(CH₃)CH₂SCH₃ Cl CF₃ Cl CH CH CH N propargyl Cl CF₃ Cl CH CH CHN Me Cl Br F CH CH CH N Et Cl Br F CH CH CH N CH(CH₃)CH₂OCH₃ Cl Br F CHCH CH N CH(CH₃)CH₂SCH₃ Cl Br F CH CH CH N propargyl Cl Br Cl CH CH CH NMe Cl Br Cl CH CH CH N Et Cl Br Cl CH CH CH N CH(CH₃)CH₂OCH₃ Cl Br Cl CHCH CH N CH(CH₃)CH₂SCH₃ Cl Br Cl CH CH CH N propargyl Cl Br Cl C—Cl CH CHCH i-Pr Me CF₃ Cl C—F CH CH CH i-Pr Me CF₃ F CH CH CH CH i-Pr Me CF₃ethynyl CH CH CH CH i-Pr Me CF₃ I CH CH CH CH i-Pr Me CF₃ SO₂Me C—Cl CHCH CH i-Pr Cl CF₃ Cl C—F CH CH CH i-Pr Cl CF₃ F CH CH CH CH i-Pr Cl CF₃ethynyl CH CH CH CH i-Pr Cl CF₃ I CH CH CH CH i-Pr Cl CF₃ SO₂Me C—Cl CHCH CH i-Pr Me Br Cl C—F CH CH CH i-Pr Me Br F CH CH CH CH i-Pr Me Brethynyl CH CH CH CH i-Pr Me Br I CH CH CH CH i-Pr Me Br SO₂Me C—Cl CH CHCH i-Pr Cl Br Cl C—F CH CH CH i-Pr Cl Br F CH CH CH CH i-Pr Cl Brethynyl CH CH CH CH i-Pr Cl Br I CH CH CH CH i-Pr Cl Br SO₂Me C—Cl CH CHN i-Pr Me CF₃ Cl C—F CH CH N i-Pr Me CF₃ F CH CH CH N i-Pr Me CF₃ethynyl CH CH CH N i-Pr Me CF₃ I CH CH CH N i-Pr Me CF₃ SO₂Me C—Cl CH CHN i-Pr Cl CF₃ Cl C—F CH CH N i-Pr Cl CF₃ F CH CH CH N i-Pr Cl CF₃ethynyl CH CH CH N i-Pr Cl CF₃ I CH CH CH N i-Pr Cl CF₃ SO₂Me C—Cl CH CHN i-Pr Me Br Cl C—F CH CH N i-Pr Me Br F CH CH CH N i-Pr Me Br ethynylCH CH CH N i-Pr Me Br I CH CH CH N i-Pr Me Br SO₂Me C—Cl CH CH N i-Pr ClBr Cl C—F CH CH N i-Pr Cl Br F CH CH CH N i-Pr Cl Br ethynyl CH CH CH Ni-Pr Cl Br I CH CH CH N i-Pr Cl Br SO₂Me CH N CH N i-Pr Me CF₃ H CH N CHN i-Pr Me CF₃ Me CH N CH N i-Pr Me CF₃ Cl CH N CH N i-Pr Cl CF₃ H CH NCH N i-Pr Cl CF₃ Me CH N CH N i-Pr Cl CF₃ Cl CH N CH N i-Pr Me CN H CH NCH N i-Pr Me CN Me CH N CH N i-Pr Me CN Cl CH N CH N i-Pr Cl CN H CH NCH N i-Pr Cl CN Me CH N CH N i-Pr Cl CN Cl CH N CH N i-Pr Me Br H CH NCH N i-Pr Me Br Me CH N CH N i-Pr Me Br Cl CH N CH N i-Pr Cl Br H CH NCH N i-Pr Cl Br Me CH N CH N i-Pr Cl Br Cl CH N CH N t-Bu Me CF₃ H CH NCH N t-Bu Me CF₃ Me CH N CH N t-Bu Me CF₃ Cl CH N CH N t-Bu Cl CF₃ H CHN CH N t-Bu Cl CF₃ Me CH N CH N t-Bu Cl CF₃ Cl CH N CH N t-Bu Me CN H CHN CH N t-Bu Me CN Me CH N CH N t-Bu Me CN Cl CH N CH N t-Bu Cl CN H CH NCH N t-Bu Cl CN Me CH N CH N t-Bu Cl CN Cl CH N CH N t-Bu Me Br H CH NCH N t-Bu Me Br Me CH N CH N t-Bu Me Br Cl CH N CH N t-Bu Cl Br H CH NCH N t-Bu Cl Br Me CH N CH N t-Bu Cl Br Cl CH CH N N i-Pr Me CF₃ H CH CHN N i-Pr Me CF₃ Me CH CH N N i-Pr Me CF₃ Cl CH CH N N i-Pr Cl CF₃ H CHCH N N i-Pr Cl CF₃ Me CH CH N N i-Pr Cl CF₃ Cl CH CH N N i-Pr Me CN H CHCH N N i-Pr Me CN Me CH CH N N i-Pr Me CN Cl CH CH N N i-Pr Cl CN H CHCH N N i-Pr Cl CN Me CH CH N N i-Pr Cl CN Cl CH CH N N i-Pr Me Br H CHCH N N i-Pr Me Br Me CH CH N N i-Pr Me Br Cl CH CH N N i-Pr Cl Br H CHCH N N i-Pr Cl Br Me CH CH N N i-Pr Cl Br Cl CH CH N N i-Pr Me CF₃ H CHCH N N i-Pr Me CF₃ Me CH CH N N i-Pr Me CF₃ Cl CH CH N N i-Pr Cl CF₃ HCH CH N N i-Pr Cl CF₃ Me CH CH N N i-Pr Cl CF₃ Cl CH CH N N i-Pr Me CN HCH CH N N i-Pr Me CN Me CH CH N N i-Pr Me CN Cl CH CH N N i-Pr Cl CN HCH CH N N i-Pr Cl CN Me CH CH N N i-Pr Cl CN Cl CH CH N N i-Pr Me Br HCH CH N N i-Pr Me Br Me CH CH N N i-Pr Me Br Cl CH CH N N i-Pr Cl Br HCH CH N N i-Pr Cl Br Me CH CH N N i-Pr Cl Br Cl

TABLE 3

R⁴ R⁶ R³ R^(9a) R^(9b) R^(9c) R⁴ R⁶ R³ R^(9a) R^(9b) R^(9c) Me CF₃ i-PrMe H H Me CF₃ t-Bu Me H H Me CF₃ i-Pr Me H Me Me CF₃ t-Bu Me H Me Me CF₃i-Pr Me Cl H Me CF₃ t-Bu Me Cl H Me CF₃ i-Pr Me Cl Me Me CF₃ t-Bu Me ClMe Me CF₃ i-Pr Me Me Me Me CF₃ t-Bu Me Me Me Cl CF₃ i-Pr Me H H Cl CF₃t-Bu Me H H Cl CF₃ i-Pr Me H Me Cl CF₃ t-Bu Me H Me Cl CF₃ i-Pr Me Cl HCl CF₃ t-Bu Me Cl H Cl CF₃ i-Pr Me Cl Me Cl CF₃ t-Bu Me Cl Me Cl CF₃i-Pr Me Me Me Cl CF₃ t-Bu Me Me Me

TABLE 4

R⁴ R⁶ R³ R^(9a) R^(9b) R^(9c) R⁴ R⁶ R³ R^(9a) R^(9b) R^(9c) Me CF₃ i-PrMe H Me Me CF₃ t-Bu Me H Me Me CF₃ i-Pr Me Me Me Me CF₃ t-Bu Me Me Me MeCF₃ i-Pr Cl H Me Me CF₃ t-Bu Cl H Me Me CF₃ i-Pr Cl Me Me Me CF₃ t-Bu ClMe Me Cl CF₃ i-Pr Me H Me Cl CF₃ t-Bu Me H Me Cl CF₃ i-Pr Me Me Me ClCF₃ t-Bu Me Me Me Cl CF₃ i-Pr Cl H Me Cl CF₃ t-Bu Cl H Me Cl CF₃ i-Pr ClMe Me Cl CF₃ t-Bu Cl Me Me

TABLE 5

R⁴ R⁵ R⁶ R³ R⁹ R⁴ R⁵ R⁶ R³ R⁹ CH₃ F CF₃ Me Cl Cl Br Cl Me Br CH₃ F CF₃Et Cl Cl Br Cl Et Br CH₃ F CF₃ i-Pr Cl Cl Br Cl i-Pr Br CH₃ F CF₃ t-BuCl Cl Br Cl t-Bu Br CH₃ F CF₃ Me Br Cl Br Br Me Cl CH₃ F CF₃ Et Br Cl BrBr Et Cl CH₃ F CF₃ i-Pr Br Cl Br Br i-Pr Cl CH₃ F CF₃ t-Bu Br Cl Br Brt-Bu Cl CH₃ F Cl Me Cl Cl Br Br Me Br CH₃ F Cl Et Cl Cl Br Br Et Br CH₃F Cl i-Pr Cl Cl Br Br i-Pr Br CH₃ F Cl t-Bu Cl Cl Br Br t-Bu Br CH₃ F ClMe Br Cl I CF₃ Me Cl CH₃ F Cl Et Br Cl I CF₃ Et Cl CH₃ F Cl i-Pr Br Cl ICF₃ i-Pr Cl CH₃ F Cl t-Bu Br Cl I CF₃ t-Bu Cl CH₃ F Br Me Cl Cl I CF₃ MeBr CH₃ F Br Et Cl Cl I CF₃ Et Br CH₃ F Br i-Pr Cl Cl I CF₃ i-Pr Br CH₃ FBr t-Bu Cl Cl I CF₃ t-Bu Br CH₃ F Br Me Br Cl I Cl Me Cl CH₃ F Br Et BrCl I Cl Et Cl CH₃ F Br i-Pr Br Cl I Cl i-Pr Cl CH₃ F Br t-Bu Br Cl I Clt-Bu Cl CH₃ Cl CF₃ Me Cl Cl I Cl Me Br CH₃ Cl CF₃ Et Cl Cl I Cl Et BrCH₃ Cl CF₃ i-Pr Cl Cl I Cl i-Pr Br CH₃ Cl CF₃ t-Bu Cl Cl I Cl t-Bu BrCH₃ Cl CF₃ Me Br Cl I Br Me Cl CH₃ Cl CF₃ Et Br Cl I Br Et Cl CH₃ Cl CF₃i-Pr Br Cl I Br i-Pr Cl CH₃ Cl CF₃ t-Bu Br Cl I Br t-Bu Cl CH₃ Cl Cl MeCl Cl I Br Me Br CH₃ Cl Cl Et Cl Cl I Br Et Br CH₃ Cl Cl i-Pr Cl Cl I Bri-Pr Br CH₃ Cl Cl t-Bu Cl Cl I Br t-Bu Br CH₃ Cl Cl Me Br Cl CF₃ CF₃ MeCl CH₃ Cl Cl Et Br Cl CF₃ CF₃ Et Cl CH₃ Cl Cl i-Pr Br Cl CF₃ CF₃ i-Pr ClCH₃ Cl Cl t-Bu Br Cl CF₃ CF₃ t-Bu Cl CH₃ Cl Br Me Cl Cl CF₃ CF₃ Me BrCH₃ Cl Br Et Cl Cl CF₃ CF₃ Et Br CH₃ Cl Br i-Pr Cl Cl CF₃ CF₃ i-Pr BrCH₃ Cl Br t-Bu Cl Cl CF₃ CF₃ t-Bu Br CH₃ Cl Br Me Br Cl CF₃ Cl Me Cl CH₃Cl Br Et Br Cl CF₃ Cl Et Cl CH₃ Cl Br i-Pr Br Cl CF₃ Cl i-Pr Cl CH₃ ClBr t-Bu Br Cl CF₃ Cl t-Bu Cl CH₃ Br CF₃ Me Cl Cl CF₃ Cl Me Br CH₃ Br CF₃Et Cl Cl CF₃ Cl Et Br CH₃ Br CF₃ i-Pr Cl Cl CF₃ Cl i-Pr Br CH₃ Br CF₃t-Bu Cl Cl CF₃ Cl t-Bu Br CH₃ Br CF₃ Me Br Cl CF₃ Br Me Cl CH₃ Br CF₃ EtBr Cl CF₃ Br Et Cl CH₃ Br CF₃ i-Pr Br Cl CF₃ Br i-Pr Cl CH₃ Br CF₃ t-BuBr Cl CF₃ Br t-Bu Cl CH₃ Br Cl Me Cl Cl CF₃ Br Me Br CH₃ Br Cl Et Cl ClCF₃ Br Et Br CH₃ Br Cl i-Pr Cl Cl CF₃ Br i-Pr Br CH₃ Br Cl t-Bu Cl ClCF₃ Br t-Bu Br CH₃ Br Cl Me Br Cl Cl Cl n-Pr Cl CH₃ Br Cl Et Br Cl Cl Cln-Bu Cl CH₃ Br Cl i-Pr Br Cl Cl Cl s-Bu Cl CH₃ Br Cl t-Bu Br Cl Cl Clt-Bu Cl CH₃ Br Br Me Cl Br F CF₃ Me Cl CH₃ Br Br Et Cl Br F CF₃ Et ClCH₃ Br Br i-Pr Cl Br F CF₃ i-Pr Cl CH₃ Br Br t-Bu Cl Br F CF₃ t-Bu ClCH₃ Br Br Me Br Br F CF₃ Me Br CH₃ Br Br Et Br Br F CF₃ Et Br CH₃ Br Bri-Pr Br Br F CF₃ i-Pr Br CH₃ Br Br t-Bu Br Br F CF₃ t-Bu Br CH₃ I CF₃ MeCl Br F Cl Me Cl CH₃ I CF₃ Et Cl Br F Cl Et Cl CH₃ I CF₃ i-Pr Cl Br F Cli-Pr Cl CH₃ I CF₃ t-Bu Cl Br F Cl t-Bu Cl CH₃ I CF₃ Me Br Br F Cl Me BrCH₃ I CF₃ Et Br Br F Cl Et Br CH₃ I CF₃ i-Pr Br Br F Cl i-Pr Br CH₃ ICF₃ t-Bu Br Br F Cl t-Bu Br CH₃ I Cl Me Cl Br F Br Me Cl CH₃ I Cl Et ClBr F Br Et Cl CH₃ I Cl i-Pr Cl Br F Br i-Pr Cl CH₃ I Cl t-Bu Cl Br F Brt-Bu Cl CH₃ I Cl Me Br Br F Br Me Br CH₃ I Cl Et Br Br F Br Et Br CH₃ ICl i-Pr Br Br F Br i-Pr Br CH₃ I Cl t-Bu Br Br F Br t-Bu Br CH₃ I Br MeCl Br Cl CF₃ Me Cl CH₃ I Br Et Cl Br Cl CF₃ Et Cl CH₃ I Br i-Pr Cl Br ClCF₃ i-Pr Cl CH₃ I Br t-Bu Cl Br Cl CF₃ t-Bu Cl CH₃ I Br Me Br Br Cl CF₃Me Br CH₃ I Br Et Br Br Cl CF₃ Et Br CH₃ I Br i-Pr Br Br Cl CF₃ i-Pr BrCH₃ I Br t-Bu Br Br Cl CF₃ t-Bu Br CH₃ CF₃ CF₃ Me Cl Br Cl Cl Me Cl CH₃CF₃ CF₃ Et Cl Br Cl Cl Et Cl CH₃ CF₃ CF₃ i-Pr Cl Br Cl Cl i-Pr Cl CH₃CF₃ CF₃ t-Bu Cl Br Cl Cl t-Bu Cl CH₃ CF₃ CF₃ Me Br Br Cl Cl Me Br CH₃CF₃ CF₃ Et Br Br Cl Cl Et Br CH₃ CF₃ CF₃ i-Pr Br Br Cl Cl i-Pr Br CH₃CF₃ CF₃ t-Bu Br Br Cl Cl t-Bu Br CH₃ CF₃ Cl Me Cl Br Cl Br Me Cl CH₃ CF₃Cl Et Cl Br Cl Br Et Cl CH₃ CF₃ Cl i-Pr Cl Br Cl Br i-Pr Cl CH₃ CF₃ Clt-Bu Cl Br Cl Br t-Bu Cl CH₃ CF₃ Cl Me Br Br Cl Br Me Br CH₃ CF₃ Cl EtBr Br Cl Br Et Br CH₃ CF₃ Cl i-Pr Br Br Cl Br i-Pr Br CH₃ CF₃ Cl t-Bu BrBr Cl Br t-Bu Br CH₃ CF₃ Br Me Cl Br Br CF₃ Me Cl CH₃ CF₃ Br Et Cl Br BrCF₃ Et Cl CH₃ CF₃ Br i-Pr Cl Br Br CF₃ i-Pr Cl CH₃ CF₃ Br t-Bu Cl Br BrCF₃ t-Bu Cl CH₃ CF₃ Br Me Br Br Br CF₃ Me Br CH₃ CF₃ Br Et Br Br Br CF₃Et Br CH₃ CF₃ Br i-Pr Br Br Br CF₃ i-Pr Br CH₃ CF₃ Br t-Bu Br Br Br CF₃t-Bu Br CH₃ Cl Cl n-Pr Cl Br Br Cl Me Cl CH₃ Cl Cl n-Bu Cl Br Br Cl EtCl CH₃ Cl Cl s-Bu Cl Br Br Cl i-Pr Cl CH₃ Cl Cl t-Bu Cl Br Br Cl t-Bu ClCl F CF₃ Me Cl Br Br Cl Me Br Cl F CF₃ Et Cl Br Br Cl Et Br Cl F CF₃i-Pr Cl Br Br Cl i-Pr Br Cl F CF₃ t-Bu Cl Br Br Cl t-Bu Br Cl F CF₃ MeBr Br Br Br Me Cl Cl F CF₃ Et Br Br Br Br Et Cl Cl F CF₃ i-Pr Br Br BrBr i-Pr Cl Cl F CF₃ t-Bu Br Br Br Br t-Bu Cl Cl F Cl Me Cl Br Br Br MeBr Cl F Cl Et Cl Br Br Br Et Br Cl F Cl i-Pr Cl Br Br Br i-Pr Br Cl F Clt-Bu Cl Br Br Br t-Bu Br Cl F Cl Me Br Br I CF₃ Me Cl Cl F Cl Et Br Br ICF₃ Et Cl Cl F Cl i-Pr Br Br I CF₃ i-Pr Cl Cl F Cl t-Bu Br Br I CF₃ t-BuCl Cl F Br Me Cl Br I CF₃ Me Br Cl F Br Et Cl Br I CF₃ Et Br Cl F Bri-Pr Cl Br I CF₃ i-Pr Br Cl F Br t-Bu Cl Br I CF₃ t-Bu Br Cl F Br Me BrBr I Cl Me Cl Cl F Br Et Br Br I Cl Et Cl Cl F Br i-Pr Br Br I Cl i-PrCl Cl F Br t-Bu Br Br I Cl t-Bu Cl Cl Cl CF₃ Me Cl Br I Cl Me Br Cl ClCF₃ Et Cl Br I Cl Et Br Cl Cl CF₃ i-Pr Cl Br I Cl i-Pr Br Cl Cl CF₃ t-BuCl Br I Cl t-Bu Br Cl Cl CF₃ Me Br Br I Br Me Cl Cl Cl CF₃ Et Br Br I BrEt Cl Cl Cl CF₃ i-Pr Br Br I Br i-Pr Cl Cl Cl CF₃ t-Bu Br Br I Br t-BuCl Cl Cl Cl Me Cl Br I Br Me Br Cl Cl Cl Et Cl Br I Br Et Br Cl Cl Cli-Pr Cl Br I Br i-Pr Br Cl Cl Cl t-Bu Cl Br I Br t-Bu Br Cl Cl Cl Me BrBr CF₃ CF₃ Me Cl Cl Cl Cl Et Br Br CF₃ CF₃ Et Cl Cl Cl Cl i-Pr Br Br CF₃CF₃ i-Pr Cl Cl Cl Cl t-Bu Br Br CF₃ CF₃ t-Bu Cl Cl Cl Br Me Cl Br CF₃CF₃ Me Br Cl Cl Br Et Cl Br CF₃ CF₃ Et Br Cl Cl Br i-Pr Cl Br CF₃ CF₃i-Pr Br Cl Cl Br t-Bu Cl Br CF₃ CF₃ t-Bu Br Cl Cl Br Me Br Br CF₃ Cl MeCl Cl Cl Br Et Br Br CF₃ Cl Et Cl Cl Cl Br i-Pr Br Br CF₃ Cl i-Pr Cl ClCl Br t-Bu Br Br CF₃ Cl t-Bu Cl Cl Br CF₃ Me Cl Br CF₃ Cl Me Br Cl BrCF₃ Et Cl Br CF₃ Cl Et Br Cl Br CF₃ i-Pr Cl Br CF₃ Cl i-Pr Br Cl Br CF₃t-Bu Cl Br CF₃ Cl t-Bu Br Cl Br CF₃ Me Br Br CF₃ Br Me Cl Cl Br CF₃ EtBr Br CF₃ Br Et Cl Cl Br CF₃ i-Pr Br Br CF₃ Br i-Pr Cl Cl Br CF₃ t-Bu BrBr CF₃ Br t-Bu Cl Cl Br Cl Me Cl Br CF₃ Br Me Br Cl Br Cl Et Cl Br CF₃Br Et Br Cl Br Cl i-Pr Cl Br CF₃ Br i-Pr Br Cl Br Cl t-Bu Cl Br CF₃ Brt-Bu Br

TABLE 6

R⁴ R⁵ R⁶ R³ R⁹ R⁴ R⁵ R⁶ R³ R⁹ CH₃ F CF₃ Me Cl Cl Br Cl Me Br CH₃ F CF₃Et Cl Cl Br Cl Et Br CH₃ F CF₃ i-Pr Cl Cl Br Cl i-Pr Br CH₃ F CF₃ t-BuCl Cl Br Cl t-Bu Br CH₃ F CF₃ Me Br Cl Br Br Me Cl CH₃ F CF₃ Et Br Cl BrBr Et Cl CH₃ F CF₃ i-Pr Br Cl Br Br i-Pr Cl CH₃ F CF₃ t-Bu Br Cl Br Brt-Bu Cl CH₃ F Cl Me Cl Cl Br Br Me Br CH₃ F Cl Et Cl Cl Br Br Et Br CH₃F Cl i-Pr Cl Cl Br Br i-Pr Br CH₃ F Cl t-Bu Cl Cl Br Br t-Bu Br CH₃ F ClMe Br Cl I CF₃ Me Cl CH₃ F Cl Et Br Cl I CF₃ Et Cl CH₃ F Cl i-Pr Br Cl ICF₃ i-Pr Cl CH₃ F Cl t-Bu Br Cl I CF₃ t-Bu Cl CH₃ F Br Me Cl Cl I CF₃ MeBr CH₃ F Br Et Cl Cl I CF₃ Et Br CH₃ F Br i-Pr Cl Cl I CF₃ i-Pr Br CH₃ FBr t-Bu Cl Cl I CF₃ t-Bu Br CH₃ F Br Me Br Cl I Cl Me Cl CH₃ F Br Et BrCl I Cl Et Cl CH₃ F Br i-Pr Br Cl I Cl i-Pr Cl CH₃ F Br t-Bu Br Cl I Clt-Bu Cl CH₃ Cl CF₃ Me Cl Cl I Cl Me Br CH₃ Cl CF₃ Et Cl Cl I Cl Et BrCH₃ Cl CF₃ i-Pr Cl Cl I Cl i-Pr Br CH₃ Cl CF₃ t-Bu Cl Cl I Cl t-Bu BrCH₃ Cl CF₃ Me Br Cl I Br Me Cl CH₃ Cl CF₃ Et Br Cl I Br Et Cl CH₃ Cl CF₃i-Pr Br Cl I Br i-Pr Cl CH₃ Cl CF₃ t-Bu Br Cl I Br t-Bu Cl CH₃ Cl Cl MeCl Cl I Br Me Br CH₃ Cl Cl Et Cl Cl I Br Et Br CH₃ Cl Cl i-Pr Cl Cl I Bri-Pr Br CH₃ Cl Cl t-Bu Cl Cl I Br t-Bu Br CH₃ Cl Cl Me Br Cl CF₃ CF₃ MeCl CH₃ Cl Cl Et Br Cl CF₃ CF₃ Et Cl CH₃ Cl Cl i-Pr Br Cl CF₃ CF₃ i-Pr ClCH₃ Cl Cl t-Bu Br Cl CF₃ CF₃ t-Bu Cl CH₃ Cl Br Me Cl Cl CF₃ CF₃ Me BrCH₃ Cl Br Et Cl Cl CF₃ CF₃ Et Br CH₃ Cl Br i-Pr Cl Cl CF₃ CF₃ i-Pr BrCH₃ Cl Br t-Bu Cl Cl CF₃ CF₃ t-Bu Br CH₃ Cl Br Me Br Cl CF₃ Cl Me Cl CH₃Cl Br Et Br Cl CF₃ Cl Et Cl CH₃ Cl Br i-Pr Br Cl CF₃ Cl i-Pr Cl CH₃ ClBr t-Bu Br Cl CF₃ Cl t-Bu Cl CH₃ Br CF₃ Me Cl Cl CF₃ Cl Me Br CH₃ Br CF₃Et Cl Cl CF₃ Cl Et Br CH₃ Br CF₃ i-Pr Cl Cl CF₃ Cl i-Pr Br CH₃ Br CF₃t-Bu Cl Cl CF₃ Cl t-Bu Br CH₃ Br CF₃ Me Br Cl CF₃ Br Me Cl CH₃ Br CF₃ EtBr Cl CF₃ Br Et Cl CH₃ Br CF₃ i-Pr Br Cl CF₃ Br i-Pr Cl CH₃ Br CF₃ t-BuBr Cl CF₃ Br t-Bu Cl CH₃ Br Cl Me Cl Cl CF₃ Br Me Br CH₃ Br Cl Et Cl ClCF₃ Br Et Br CH₃ Br Cl i-Pr Cl Cl CF₃ Br i-Pr Br CH₃ Br Cl t-Bu Cl ClCF₃ Br t-Bu Br CH₃ Br Cl Me Br Cl Cl Cl n-Pr Cl CH₃ Br Cl Et Br Cl Cl Cln-Bu Cl CH₃ Br Cl i-Pr Br Cl Cl Cl s-Bu Cl CH₃ Br Cl t-Bu Br Cl Cl Clt-Bu Cl CH₃ Br Br Me Cl Br F CF₃ Me Cl CH₃ Br Br Et Cl Br F CF₃ Et ClCH₃ Br Br i-Pr Cl Br F CF₃ i-Pr Cl CH₃ Br Br t-Bu Cl Br F CF₃ t-Bu ClCH₃ Br Br Me Br Br F CF₃ Me Br CH₃ Br Br Et Br Br F CF₃ Et Br CH₃ Br Bri-Pr Br Br F CF₃ i-Pr Br CH₃ Br Br t-Bu Br Br F CF₃ t-Bu Br CH₃ I CF₃ MeCl Br F Cl Me Cl CH₃ I CF₃ Et Cl Br F Cl Et Cl CH₃ I CF₃ i-Pr Cl Br F Cli-Pr Cl CH₃ I CF₃ t-Bu Cl Br F Cl t-Bu Cl CH₃ I CF₃ Me Br Br F Cl Me BrCH₃ I CF₃ Et Br Br F Cl Et Br CH₃ I CF₃ i-Pr Br Br F Cl i-Pr Br CH₃ ICF₃ t-Bu Br Br F Cl t-Bu Br CH₃ I Cl Me Cl Br F Br Me Cl CH₃ I Cl Et ClBr F Br Et Cl CH₃ I Cl i-Pr Cl Br F Br i-Pr Cl CH₃ I Cl t-Bu Cl Br F Brt-Bu Cl CH₃ I Cl Me Br Br F Br Me Br CH₃ I Cl Et Br Br F Br Et Br CH₃ ICl i-Pr Br Br F Br i-Pr Br CH₃ I Cl t-Bu Br Br F Br t-Bu Br CH₃ I Br MeCl Br Cl CF₃ Me Cl CH₃ I Br Et Cl Br Cl CF₃ Et Cl CH₃ I Br i-Pr Cl Br ClCF₃ i-Pr Cl CH₃ I Br t-Bu Cl Br Cl CF₃ t-Bu Cl CH₃ I Br Me Br Br Cl CF₃Me Br CH₃ I Br Et Br Br Cl CF₃ Et Br CH₃ I Br i-Pr Br Br Cl CF₃ i-Pr BrCH₃ I Br t-Bu Br Br Cl CF₃ t-Bu Br CH₃ CF₃ CF₃ Me Cl Br Cl Cl Me Cl CH₃CF₃ CF₃ Et Cl Br Cl Cl Et Cl CH₃ CF₃ CF₃ i-Pr Cl Br Cl Cl i-Pr Cl CH₃CF₃ CF₃ t-Bu Cl Br Cl Cl t-Bu Cl CH₃ CF₃ CF₃ Me Br Br Cl Cl Me Br CH₃CF₃ CF₃ Et Br Br Cl Cl Et Br CH₃ CF₃ CF₃ i-Pr Br Br Cl Cl i-Pr Br CH₃CF₃ CF₃ t-Bu Br Br Cl Cl t-Bu Br CH₃ CF₃ Cl Me Cl Br Cl Br Me Cl CH₃ CF₃Cl Et Cl Br Cl Br Et Cl CH₃ CF₃ Cl i-Pr Cl Br Cl Br i-Pr Cl CH₃ CF₃ Clt-Bu Cl Br Cl Br t-Bu Cl CH₃ CF₃ Cl Me Br Br Cl Br Me Br CH₃ CF₃ Cl EtBr Br Cl Br Et Br CH₃ CF₃ Cl i-Pr Br Br Cl Br i-Pr Br CH₃ CF₃ Cl t-Bu BrBr Cl Br t-Bu Br CH₃ CF₃ Br Me Cl Br Br CF₃ Me Cl CH₃ CF₃ Br Et Cl Br BrCF₃ Et Cl CH₃ CF₃ Br i-Pr Cl Br Br CF₃ i-Pr Cl CH₃ CF₃ Br t-Bu Cl Br BrCF₃ t-Bu Cl CH₃ CF₃ Br Me Br Br Br CF₃ Me Br CH₃ CF₃ Br Et Br Br Br CF₃Et Br CH₃ CF₃ Br i-Pr Br Br Br CF₃ i-Pr Br CH₃ CF₃ Br t-Bu Br Br Br CF₃t-Bu Br CH₃ Cl Cl n-Pr Cl Br Br Cl Me Cl CH₃ Cl Cl n-Bu Cl Br Br Cl EtCl CH₃ Cl Cl s-Bu Cl Br Br Cl i-Pr Cl CH₃ Cl Cl t-Bu Cl Br Br Cl t-Bu ClCl F CF₃ Me Cl Br Br Cl Me Br Cl F CF₃ Et Cl Br Br Cl Et Br Cl F CF₃i-Pr Cl Br Br Cl i-Pr Br Cl F CF₃ t-Bu Cl Br Br Cl t-Bu Br Cl F CF₃ MeBr Br Br Br Me Cl Cl F CF₃ Et Br Br Br Br Et Cl Cl F CF₃ i-Pr Br Br BrBr i-Pr Cl Cl F CF₃ t-Bu Br Br Br Br t-Bu Cl Cl F Cl Me Cl Br Br Br MeBr Cl F Cl Et Cl Br Br Br Et Br Cl F Cl i-Pr Cl Br Br Br i-Pr Br Cl F Clt-Bu Cl Br Br Br t-Bu Br Cl F Cl Me Br Br I CF₃ Me Cl Cl F Cl Et Br Br ICF₃ Et Cl Cl F Cl i-Pr Br Br I CF₃ i-Pr Cl Cl F Cl t-Bu Br Br I CF₃ t-BuCl Cl F Br Me Cl Br I CF₃ Me Br Cl F Br Et Cl Br I CF₃ Et Br Cl F Bri-Pr Cl Br I CF₃ i-Pr Br Cl F Br t-Bu Cl Br I CF₃ t-Bu Br Cl F Br Me BrBr I Cl Me Cl Cl F Br Et Br Br I Cl Et Cl Cl F Br i-Pr Br Br I Cl i-PrCl Cl F Br t-Bu Br Br I Cl t-Bu Cl Cl Cl CF₃ Me Cl Br I Cl Me Br Cl ClCF₃ Et Cl Br I Cl Et Br Cl Cl CF₃ i-Pr Cl Br I Cl i-Pr Br Cl Cl CF₃ t-BuCl Br I Cl t-Bu Br Cl Cl CF₃ Me Br Br I Br Me Cl Cl Cl CF₃ Et Br Br I BrEt Cl Cl Cl CF₃ i-Pr Br Br I Br i-Pr Cl Cl Cl CF₃ t-Bu Br Br I Br t-BuCl Cl Cl Cl Me Cl Br I Br Me Br Cl Cl Cl Et Cl Br I Br Et Br Cl Cl Cli-Pr Cl Br I Br i-Pr Br Cl Cl Cl t-Bu Cl Br I Br t-Bu Br Cl Cl Cl Me BrBr CF₃ CF₃ Me Cl Cl Cl Cl Et Br Br CF₃ CF₃ Et Cl Cl Cl Cl i-Pr Br Br CF₃CF₃ i-Pr Cl Cl Cl Cl t-Bu Br Br CF₃ CF₃ t-Bu Cl Cl Cl Br Me Cl Br CF₃CF₃ Me Br Cl Cl Br Et Cl Br CF₃ CF₃ Et Br Cl Cl Br i-Pr Cl Br CF₃ CF₃i-Pr Br Cl Cl Br t-Bu Cl Br CF₃ CF₃ t-Bu Br Cl Cl Br Me Br Br CF₃ Cl MeCl Cl Cl Br Et Br Br CF₃ Cl Et Cl Cl Cl Br i-Pr Br Br CF₃ Cl i-Pr Cl ClCl Br t-Bu Br Br CF₃ Cl t-Bu Cl Cl Br CF₃ Me Cl Br CF₃ Cl Me Br Cl BrCF₃ Et Cl Br CF₃ Cl Et Br Cl Br CF₃ i-Pr Cl Br CF₃ Cl i-Pr Br Cl Br CF₃t-Bu Cl Br CF₃ Cl t-Bu Br Cl Br CF₃ Me Br Br CF₃ Br Me Cl Cl Br CF₃ EtBr Br CF₃ Br Et Cl Cl Br CF₃ i-Pr Br Br CF₃ Br i-Pr Cl Cl Br CF₃ t-Bu BrBr CF₃ Br t-Bu Cl Cl Br Cl Me Cl Br CF₃ Br Me Br Cl Br Cl Et Cl Br CF₃Br Et Br Cl Br Cl i-Pr Cl Br CF₃ Br i-Pr Br Cl Br Cl t-Bu Cl Br CF₃ Brt-Bu Br

As shown in Scheme 7 and further illustrated in Examples 4 and 5, thebenzoxazines of Formula 10a-b such as those listed in Tables 7 and 8 areuseful for preparing the compounds of Formula I, including those listedin Tables 2 and 5.

TABLE 7 10a

W X Y Z R⁴ R⁶ R⁹ CH CH CH CH Me CF₃ Me CH CH CH CH Cl CF₃ Me CH CH CH CHBr CF₃ Me CH CH CH CH Me Cl Me CH CH CH CH Cl Cl Me CH CH CH CH Br Cl MeCH CH CH CH Me Br Me CH CH CH CH Cl Br Me CH CH CH CH Br Br Me CH CH CHCH Me CN Me CH CH CH CH Cl CN Me CH CH CH CH Br CN Me CH CH CH CH Me CF₃F CH CH CH CH Cl CF₃ F CH CH CH CH Br CF₃ F CH CH CH CH Me Cl F CH CH CHCH Cl Cl F CH CH CH CH Br Cl F CH CH CH CH Me Br F CH CH CH CH Cl Br FCH CH CH CH Br Br F CH CH CH CH Me CN F CH CH CH CH Cl CN F CH CH CH CHBr CN F CH CH CH CH Me CF₃ Cl CH CH CH CH Cl CF₃ Cl CH CH CH CH Br CF₃Cl CH CH CH CH Me Cl Cl CH CH CH CH Cl Cl Cl CH CH CH CH Br Cl Cl CH CHCH CH Me Br Cl CH CH CH CH Cl Br Cl CH CH CH CH Br Br Cl CH CH CH CH MeCN Cl CH CH CH CH Cl CN Cl CH CH CH CH Br CN Cl CH CH CH CH Me CF₃ Br CHCH CH CH Cl CF₃ Br CH CH CH CH Br CF₃ Br CH CH CH CH Me Cl Br CH CH CHCH Cl Cl Br CH CH CH CH Br Cl Br CH CH CH CH Me Br Br CH CH CH CH Cl BrBr CH CH CH CH Br Br Br CH CH CH CH Me CN Br CH CH CH CH Cl CN Br CH CHCH CH Br CN Br CH CH CH CH Me CF₃ CN CH CH CH CH Cl CF₃ CN CH CH CH CHBr CF₃ CN CH CH CH CH Me Cl CN CH CH CH CH Cl Cl CN CH CH CH CH Br Cl CNCH CH CH CH Me Br CN CH CH CH CH Cl Br CN CH CH CH CH Br Br CN CH CH CHCH Me CN CN CH CH CH CH Cl CN CN CH CH CH CH Br CN CN CH CH CH N Me CF₃Me CH CH CH N Cl CF₃ Me CH CH CH N Br CF₃ Me CH CH CH N Me Cl Me CH CHCH N Cl Cl Me CH CH CH N Br Cl Me CH CH CH N Me Br Me CH CH CH N Cl BrMe CH CH CH N Br Br Me CH CH CH N Me CN Me CH CH CH N Cl CN Me CH CH CHN Br CN Me CH CH CH N Me CF₃ F CH CH CH N Cl CF₃ F CH CH CH N Br CF₃ FCH CH CH N Me Cl F CH CH CH N Cl Cl F CH CH CH N Br Cl F CH CH CH N MeBr F CH CH CH N Cl Br F CH CH CH N Br Br F CH CH CH N Me CN F CH CH CH NCl CN F CH CH CH N Br CN F CH CH CH N Me CF₃ Cl CH CH CH N Cl CF₃ Cl CHCH CH N Br CF₃ Cl CH CH CH N Me Cl Cl CH CH CH N Cl Cl Cl CH CH CH N BrCl Cl CH CH CH N Me Br Cl CH CH CH N Cl Br Cl CH CH CH N Br Br Cl CH CHCH N Me CN Cl CH CH CH N Cl CN Cl CH CH CH N Br CN Cl CH CH CH N Me CF₃Br CH CH CH N Cl CF₃ Br CH CH CH N Br CF₃ Br CH CH CH N Me Cl Br CH CHCH N Cl Cl Br CH CH CH N Br Cl Br CH CH CH N Me Br Br CH CH CH N Cl BrBr CH CH CH N Br Br Br CH CH CH N Me CN Br CH CH CH N Cl CN Br CH CH CHN Br CN Br CH CH CH N Me CF₃ CN CH CH CH N Cl CF₃ CN CH CH CH N Br CF₃CN CH CH CH N Me Cl CN CH CH CH N Cl Cl CN CH CH CH N Br Cl CN CH CH CHN Me Br CN CH CH CH N Cl Br CN CH CH CH N Br Br CN CH CH CH N Me CN CNCH CH CH N Cl CN CN CH CH CH N Br CN CN C—Cl CH CH CH Me CF₃ Cl C—F CHCH CH Me CF₃ F CH CH CH CH Me CF₃ ethnyl CH CH CH CH Me CF₃ I CH CH CHCH Me CF₃ SO₂Me C—Cl CH CH CH Cl CF₃ Cl C—F CH CH CH Cl CF₃ F CH CH CHCH Cl CF₃ ethnyl CH CH CH CH Cl CF₃ I CH CH CH CH Cl CF₃ SO₂Me C—Cl CHCH CH Me Br Cl C—F CH CH CH Me Br F CH CH CH CH Me Br ethnyl CH CH CH CHMe Br I CH CH CH CH Me Br SO₂Me C—Cl CH CH CH Cl Br Cl C—F CH CH CH ClBr F CH CH CH CH Cl Br ethnyl CH CH CH CH Cl Br I CH CH CH CH Cl BrSO₂Me C—Cl CH CH N Me CF₃ Cl C—F CH CH N Me CF₃ F CH CH CH N Me CF₃ethnyl CH CH CH N Me CF₃ I CH CH CH N Me CF₃ SO₂Me C—Cl CH CH N Cl CF₃Cl C—F CH CH N Cl CF₃ F CH CH CH N Cl CF₃ ethnyl CH CH CH N Cl CF₃ I CHCH CH N Cl CF₃ SO₂Me C—Cl CH CH N Me Br Cl C—F CH CH N Me Br F CH CH CHN Me Br ethnyl CH CH CH N Me Br I CH CH CH N Me Br SO₂Me C—Cl CH CH N ClBr Cl C—F CH CH N Cl Br F CH CH CH N Cl Br ethnyl CH CH CH N Cl Br I CHCH CH N Cl Br SO₂Me CH N CH N Me CF₃ H CH N CH N Me CF₃ Me CH N CH N MeCF₃ Cl CH N CH N Cl CF₃ H CH N CH N Cl CF₃ Me CH N CH N Cl CF₃ Cl CH NCH N Me CN H CH N CH N Me CN Me CH N CH N Me CN Cl CH N CH N Cl CN H CHN CH N Cl CN Me CH N CH N Cl CN Cl CH N CH N Me Br H CH N CH N Me Br MeCH N CH N Me Br Cl CH N CH N Cl Br H CH N CH N Cl Br Me CH N CH N Cl BrCl CH CH N N Me CF₃ H CH CH N N Me CF₃ Me CH CH N N Me CF₃ Cl CH CH N NCl CF₃ H CH CH N N Cl CF₃ Me CH CH N N Cl CF₃ Cl CH CH N N Me CN H CH CHN N Me CN Me CH CH N N Me CN Cl CH CH N N Cl CN H CH CH N N Cl CN Me CHCH N N Cl CN Cl CH CH N N Me Br H CH CH N N Me Br Me CH CH N N Me Br ClCH CH N N Cl Br H CH CH N N Cl Br Me CH CH N N Cl Br Cl CH CH N N Me CF₃H CH CH N N Me CF₃ Me CH CH N N Me CF₃ Cl CH CH N N Cl CF₃ H CH CH N NCl CF₃ Me CH CH N N Cl CF₃ Cl CH CH N N Me CN H CH CH N N Me CN Me CH CHN N Me CN Cl CH CH N N Cl CN H CH CH N N Cl CN Me CH CH N N Cl CN Cl CHCH N N Me Br H CH CH N N Me Br Me CH CH N N Me Br Cl CH CH N N Cl Br HCH CH N N Cl Br Me CH CH N N Cl Br Cl

TABLE 8 10b

R⁴ R⁵ R⁶ R⁹ R⁴ R⁵ R⁶ R⁹ CH₃ F CF₃ Cl Cl Br Cl Br CH₃ F CF₃ Br Cl Br BrCl CH₃ F Cl Cl Cl Br Br Br CH₃ F Cl Br Cl I CF₃ Cl CH₃ F Br Cl Cl I CF₃Br CH₃ F Br Br Cl I Cl Cl CH₃ Cl CF₃ Cl Cl I Cl Br CH₃ Cl CF₃ Br Cl I BrCl CH₃ Cl Cl Cl Cl I Br Br CH₃ Cl Cl Br Cl CF₃ CF₃ Cl CH₃ Cl Br Cl ClCF₃ CF₃ Br CH₃ Cl Br Br Cl CF₃ Cl Cl CH₃ Br CF₃ Cl Cl CF₃ Cl Br CH₃ BrCF₃ Br Cl CF₃ Br Cl CH₃ Br Cl Cl Cl CF₃ Br Br CH₃ Br Cl Br Cl Cl Cl ClCH₃ Br Br Cl Br F CF₃ Cl CH₃ Br Br Br Br F CF₃ Br CH₃ I CF₃ Cl Br F ClCl CH₃ I CF₃ Br Br F Cl Br CH₃ I Cl Cl Br F Br Cl CH₃ I Cl Br Br F Br BrCH₃ I Br Cl Br Cl CF₃ Cl CH₃ I Br Br Br Cl CF₃ Br CH₃ CF₃ CF₃ Cl Br ClCl Cl CH₃ CF₃ CF₃ Br Br Cl Cl Br CH₃ CF₃ Cl Cl Br Cl Br Cl CH₃ CF₃ Cl BrBr Cl Br Br CH₃ CF₃ Br Cl Br Br CF₃ Cl CH₃ CF₃ Br Br Br Br CF₃ Br CH₃ ClCl Cl Br Br Cl Cl Cl F CF₃ Cl Br Br Cl Br Cl F CF₃ Br Br Br Br Cl Cl FCl Cl Br Br Br Br Cl F Cl Br Br I CF₃ Cl Cl F Br Cl Br I CF₃ Br Cl F BrBr Br I Cl Cl Cl Cl CF₃ Cl Br I Cl Br Cl Cl CF₃ Br Br I Br Cl Cl Cl ClCl Br I Br Br Cl Cl Cl Br Br CF₃ CF₃ Cl Cl Cl Br Cl Br CF₃ CF₃ Br Cl ClBr Br Br CF₃ Cl Cl Cl Br CF₃ Cl Br CF₃ Cl Br Cl Br CF₃ Br Br CF₃ Br ClCl Br Cl Cl Br CF₃ Br BrFormulation/Utility

Compounds of this invention will generally be used as a formulation orcomposition with an agriculturally suitable carrier comprising at leastone of a liquid diluent, a solid diluent or a surfactant. Theformulation or composition ingredients are selected to be consistentwith the physical properties of the active ingredient, mode ofapplication and environmental factors such as soil type, moisture andtemperature. Useful formulations include liquids such as solutions(including emulsifiable concentrates), suspensions, emulsions (includingmicroemulsions and/or suspoemulsions) and the like which optionally canbe thickened into gels. Useful formulations further include solids suchas dusts, powders, granules, pellets, tablets, films, and the like whichcan be water-dispersible (“wettable”) or water-soluble. Activeingredient can be (micro)encapsulated and further formed into asuspension or solid formulation; alternatively the entire formulation ofactive ingredient can be encapsulated (or “overcoated”). Encapsulationcan control or delay release of the active ingredient. Sprayableformulations can be extended in suitable media and used at spray volumesfrom about one to several hundred liters per hectare. High-strengthcompositions are primarily used as intermediates for furtherformulation.

The formulations will typically contain effective amounts of activeingredient, diluent and surfactant within the following approximateranges that add up to 100 percent by weight.

Weight Percent Active Ingredient Dilutent Surfactant Water-Dispersible  5-90  0-94 1-15 and Water-soluble Granules, Tablets and Powders.Suspensions, Emulsions,   5-50 40-95 0-15 Solutions (includingEmulsifiable Concentrates) Dusts   1-25 70-99 0-5 Granules and 0.01-99 5-99.99 0-15 Pellets High Strength   90-99  0-10 0-2 Compositions

Typical solid diluents are described in Watkins, et al., Handbook ofInsecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books,Caldwell, N.J. Typical liquid diluents are described in Marsden,Solvents Guide, 2nd Ed., Interscience, New York, 1950. McCutcheon'sDetergents and Emulsifiers Annual, Allured Publ. Corp., Ridgewood, N.J.,as well as Sisely and Wood, Encyclopedia of Surface Active Agents,Chemical Publ. Co., Inc., New York, 1964, list surfactants andrecommended uses. All formulations can contain minor amounts ofadditives to reduce foam, caking, corrosion, microbiological growth andthe like, or thickeners to increase viscosity.

Surfactants include, for example, polyethoxylated alcohols,polyethoxylated alkylphenols, polyethoxylated sorbitan fatty acidesters, dlalkyl sulfosuccinates, alkyl sulfates, alkylbenzenesulfonates, organosilicones, N,N-dialkyltaurates, lignin sulfonates,naphthalene sulfonate formaldehyde condensates, polycarboxylates, andpolyoxyethylene/polyoxypropylene block copolymers. Solid diluentsinclude, for example, clays such as bentonite, montmorillonite,attapulgite and kaolin, starch, sugar, silica, talc, diatomaceous earth,urea, calcium carbonate, sodium carbonate and bicarbonate, and sodiumsulfate. Liquid diluents include, for example, water,N,N-dimethylformamide, dimethyl sulfoxide, N-alkylpyrrolidone, ethyleneglycol, polypropylene glycol, paraffins, alkylbenzenes,alkylnaphthalenes, oils of olive, castor, unseed, tung, sesame, corn,peanut, cotton-seed, soybean, rape-seed and coconut, fatty acid esters,ketones such as cyclohexanone, 2-heptanone, isophorone and4-hydroxy-4-methyl-2-pentanone, and alcohols such as methanol,cyclohexanol, decanol and tetrahydrofurfuryl alcohol.

Solutions, including emulsifiable concentrates, can be prepared bysimply mixing the ingredients. Dusts and powders can be prepared byblending and, usually, grinding as in a hammer mill or fluid-energymill. Suspensions are usually prepared by wet-milling; see, for example,U.S. Pat. No. 3,060,084. Granules and pellets can be prepared byspraying the active material upon preformed granular carriers or byagglomeration techniques. See Browning, “Agglomeration”, ChemicalEngineering, Dec. 4, 1967, pp 147-48, Perry's Chemical Engineer'sHandbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 andfollowing, and PCT Publication WO 91/13546. Pellets can be prepared asdescribed in U.S. Pat. No. 4,172,714. Water-dispersible andwater-soluble granules can be prepared as taught in U.S. Pat. No.4,144,050, U.S. Pat. No. 3,920,442 and DE 3,246,493. Tablets can beprepared as taught in U.S. Pat. No. 5,180,557, U.S. Pat. No. 3,232,701and U.S. Pat. No. 5,208,030. Films can be prepared as taught in GB2,095,558 and U.S. Pat. No. 3,299,566.

For further information regarding the art of formulation, see T. S.Woods, “The Formulator's Toolbox—Product Forms for Modern Agriculture”in Pesticide Chemistry and Bioscience, The Food-Environment Challenge,T. Brooks and T. R. Roberts, Eds., Proceedings of the 9th InternationalCongress on Pesticide Chemistry, The Royal Society of Chemistry,Cambridge, 1999, pp. 120-133. See also U.S. Pat. No. 3,235,361, Col. 6,line 16 through Col. 7, line 19 and Examples 10-41; U.S. Pat. No.3,309,192, Col. 5, line 43 through Col. 7, line 62 and Examples 8, 12,15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182;U.S. Pat. No. 2,891,855, Col. 3, line 66 through Col. 5, line 17 andExamples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons,Inc., New York, 1961, pp 81-96; and Hance et al., Weed Control Handbook,8th Ed, Blackball Scientific Publications, Oxford, 1989.

In the following Examples, all percentages are by weight, and allformulations are prepared in conventional ways. Compound numbers referto compounds in index Table A.

Example A Wettable Powder

Compound 214 65.0% dodecylphenol polyethylene  2.0% glycol ether sodiumligninsulfonate  4.0% sodium silicoaluminate  6.0% montmorillonite(calcined) 23.0%

Example B Granule

Compound 214 10.0% attapulgite granules (low volatile matter, 90.0%0.71/0.30 mm; U.S.S. No. 25-50 sieves)

Example C Extruded Pellet

Compound 214 25.0% anhydrous sodium sulfate 10.0% crude calciumligninsulfonate  5.0% sodium alkylnaphtalenesulfonate  1.0%calcium/magnesium bentonite 59.0%

Example D Emulsifiable Concentrate

Compound 214 20.0% blend of oil soluble sulfonates 10.0% andpolyoxyethylene ethers isophorone 70.0%

Example E Granule

Compound 214  0.5% cellulose  2.5% lactose  4.0% cornmeal 93.0%

Compounds of this invention are characterized by favorable metabolicand/or soil residual patterns and exhibit activity controlling aspectrum of agronomic and non-agronomic invertebrate pests. (In thecontext of this disclosure “invertebrate pest control” means inhibitionof invertebrate pest development (including mortality) that causessignificant reduction in feeding or other injury or damage caused by thepest; related expressions are defined analogously. As referred to inthis disclosure, the term “invertebrate pest” includes arthropods,gastropods and nematodes of economic importance as pests. The term“arthropod” includes insects, mites, spiders, scorpions, centipedes,millipedes, pill bugs and symphylans. The term “gastropod” includessnails, slugs and other Stylommatophora. The term “nematode” includesall of the helminths, such as: roundworms, heartworms, and phytophagousnematodes (Nematode), flukes (Tematoda), Acanthocephala, and tapeworms(Cestoda). Those skilled in the art will recognize that not allcompounds are equally effective against all pests. Compounds of thisinvention display activity against economically important agronomic,forest, greenhouse, nursery, ornamentals, food and fiber, public andanimal health, domestic and commercial structure, household, and storedproduct pests. These include larvae of the order Lepidoptem, such asarmyworms, cutworms, loopers, and heliothines in the family Noctuidae(e.g., fall armyworm (Spodoptera fugiperda J. E. Smith), beet armywom(Spodoptera exigua Hübner), black cutworm (Agrotis ipsilon Hufnagel),cabbage looper (Trichoplusia ni Hübner), tobacco budworm (Heliothicvirescens Fabricius)); borers, casebearers, webworms, coneworms,cabbageworms and skeletonizers from the family Pyralidae (e.g. Europeancorn borer (Ostrinia nubilalis Hübner), navel orangeworm (Amyeloistransitella Walker), corn root webworm (Crambus caliginosellus Clemens),sod webworm (Herpetogramma licarsisalis Walker)); leafrollers, budworms,seed worms, and fruit worms in the family Tortricidae (e.g., codlingmoth (Cydia pomonella Linnaeus), grape berry moth (Endopiza viteanaClemens), oriental fruit moth (Grapholita molesta Busck)); and manyother economically important lepidoptera (e.g., diamondback moth(Plutella xylostella Linnaeus), pink bollworm (Pectinophora gossypiellaSaunders), gypsy moth (Lymantria dispar Linnaeus)); nymphs and adults ofthe order Blattodea including cockroaches from the families Blattellidaeand Blattidae (e.g., oriental cockroach (Blatta orientalis Linnaeus),Asian cockroach (Blatella asahinai Mizukubo), German cockroach (Blatellagermanica Linnaeus), brownbanded cockroach (Supella longipalpaFabricius), American cockroach (Periplaneta american Linnaeus), browncockroach (Periplaneta brunnea Burmeister), Madeira cockroach(Leucophaea maderae Fabricius)); foliar feeding larvae and adults of theorder Coleoptera including weevils from the families Anthridbidae,Bruchidae, and Curculionidae (e.g., boll weevil (Anthonomus grandisBoheman), rice water weevil (Lissorhoptrus oryzophilus Kuschel), granaryweevil (Stiophilus granarius Linnaeus), rice weevil (Sitophilus oryzaeLinnaeus)); flea beetles, cucumber beetles, rootworms, leaf beetles,potato beetles, and leafminers in the family Chrysomelidae (e.g.,Colorado potato beetle (Leptinotarsa decemlineata Say), western cornrootworm (Diabrotica virgifera virgifera LeConte)); chafers and otherbeetles from the family Scaribaeidae (e.g., Japanese beetles (Popilliajaponica Newman) and European chafer (Rhizotrogus majalis Razoumowsky));carpet beetles from the family Dermestidae; wireworms from the familyElateridae; bark beetles from the family Scolytidae and flour beetlesfrom the family Tenebrionidae. In addition it includes: adults andlarvae of the order Dermaptera including earwigs from the familyForficulidae (e.g., European earwig (Forficula auricularia Linnaeus),black earwig (Chelisoches morio Fabricius)); adults and nymphs of theorders Hemiptera and Homoptera such as, plant bugs from the familyMiridae, cicadas from the family Cicadidae, leafhoppers (e.g. Empoascaspp.) from the family Cicadellidae, planthoppers from the familiesFulgoroidae and Delphacidae, treehoppers from the family Membracidae,psyllids from the family Psyllidae, whiteflies from the familyAleyrodidae, aphids from the family Aphididae, phylloxera from thefamily Phylloxeridae, mealybugs from the family Pseudococcidae, scalesfrom the families Coccidae, Diaspididae and Margarodidae, lace bugs fromthe family Tingidae, stink bugs from the family Pentatomidae, cinch bugs(e.g., Blissus spp.) and other seed bugs from the family Lygaeidae,spittlebugs from the family Cercopidae squash bugs from the familyCoreidae, and red bugs and cotton stainers from the familyPyrrhocoridae. Also included are adults and larvae of the order Acari(mites) such as spider mites and red mites in the family Tetranychidae(e.g., European red mite (Panonychus ulmi Koch), two spotted spider mite(Tetranychus urticae Koch), McDaniel mite (Tetranychus mcdanieliMcGregor)), flat mites in the family Temipalpidae (e.g., citrus flatmite (Brevipalpus lewisi McGregor)), rust and bud mites in the familyEriophyidae and other foliar feeding mites and mites important in humanand animal health, i.e. dust mites in the family Epidermoptidae,follicle mites in the family Demodicidae, grain mites in the familyGlycycphagidae, ticks in the order Ixodidae (e.g., deer tick (Ixodesscapularis Say), Australian paralysis tick (Ixodes holocyclus Neumann),American dog tick (Dermacentor variabilis Say), lone star tick(Amblyomma americanum Linnaes) and scab and itch mites in the familiesPsoroptidae, Pyemotidae, and Sarcoptidae; adults and immatures of theorder Orthoptera including grasshoppers, locusts and crickets (e.g.,migratory grasshoppers (e.g., Melanophus sanguinipes Fabricius, M.differentalis Thomas), American grasshoppers (e.g., Schistocercaamericana Drury), desert locust (Schistocerca gregaria Forskal),migratory locust (Locusta migratoria Linnaeus), house cricket (Achetadomesticus Linnaeus), mole crickets (Gryllotalpa spp.)); adults andimmatures of the order Diptera including leafminers, midges, fruit flies(Tephritidae), frit flies (e.g., Oscinella frit Linnaues), soil maggots,house flies (e.g., Musa domestica Linnaeus), lesser house flies (e.g.,Fannia canicularis Linnaeus, F. femoralis Stein), stable flies (e.g.,Stomoxys calcitrans Linnaeus), face flies, horn flies, blow flies (e.g.,Chrysomya spp., Phormia spp.), and other muscoid fly pests, horse flies(e.g., Tabanus spp.), bot flies (e.g., Gastrophilus spp., Oestrus spp.),cattle grubs (e.g., Hypoderma spp.), deer flies (e.g., Chrysops spp.),keds (e.g., Melophagus ovinus Linnaeus) and other Brachycera, mosquitoes(e.g., Aedes spp., Anopheles spp., Culex spp.), black flies (e.g.,Prostmulium spp., Simulium spp.), biting midges, sand flies, sciarids,and other Nematocera; adults and immatures of the order Thysanopteraincluding onion thrips (Thrips tabaci Lindeman) and other foliar feedingthrips; insect pests of the order Hymenoptera including ants (e.g., redcarpenter ant (Camponotus ferrugineus Fabricius), black carpenter ant(Camponotus pennsylvanicus De Geer), Pharaoh ant (Monomorium pharaonisLinnaeus), little fire ant (Wasmannia auropunctata Roger), fire ant(Solenopsis geminata Fabricius), red imported fire ant (Solenopsisinvicta Buren), Argentine ant (Iridomyrmex humilis Mayr), crazy ant(Paratrechina longicornis Latreille), pavement ant (Tetramoriumcaespitun Linnaeus), cornfield ant (Lasius alienus Förster), odoroushouse ant (Tapinoma sessile Say)), bees (including carpenter bees),hornets, yellow jackets and wasps; insect pests of the order Isopteraincluding the eastern subterranean termite (Reticulitermes flavipesKollar), western subterranean termite (Reticulitermes hesperus Banks),Formosan subterranean termite (Coptotermes formosanus Shiraki), WestIndian drywood termite (Incisitermes immigrans Snyder) and othertermites of economic importance; insect pests of the order Thysanurasuch as sliverfish (Lepisma saccharina Linnaeus) and firebrat (Thermpbiadomestica Packard); insect pests of the order Mallophaga and includingthe head louse (Pediculus humanus capitis De Geer), body louse(Pediculus humanus humanus Linnaeus), chicken body louse (Menacanthusstramineus Nitszch), dog biting louse (Trichodectes canis De Geer),fluff louse (Goniocotes gallinae De Geer), sheep body louse (Bovicolaovis Schrank), short-nosed cattle louse (Haematopinus eurysternusNitszch), long-nosed cattle louse (Linognathus vituli Linnaeus) andother sucking and chewing parasitic lice that attack man and animals;insect pests of the order Siphonoptera including the oriental rat flea(Xenopsylla cheopis Rothschild), cat flea (Ctenocephalides felisBouche), dog flea (Ctenocephalides canis Curtis), hen flea(Ctenocephalides gallinae Schrank), sticktight flea (Echidnophagagallinacea Westwood), human flea (Pulex irritans Linnaeus) and otherfleas afflicting mammals and birds. Additional arthropod pests coveredinclude: spiders in the order Araneae such as the brown recluse spider(Loxosceles reclusa Gertsch & Mulaik) and the black widow spider(Latrodectus mactans Fabricius), and centipedes in the orderScutigeromorpha such as the house centipede (Scutigera coleoptrataLinnaeus). Activity also includes members of the Classes Nematoda,Cestoda, Trematoda, and Acanthocephala including economically importantmembers of the orders Strongylida, Ascaridida, Oxyurida, Rhabditida,Spirurida, and Enoplida such as but not limited to economicallyimportant agricultural pests (i.e. root knot nematodes in the genusMeloidogyne, lesion nematodes in the genus Pratylenchus, stubby rootnematodes in the genus Trichodurus, etc.) and animal and human healthpests (i.e. all economiccally important flukes, tapeworms, androundworms, such as Strongylus vulgaris in horses, Toxocara canis indogs, Haemonchus contortus in sheep, Dirofilaria immitis Leidy in dogs,Anoplocephala perfoliata in horses, Fasciola hepatica Linnaeus inruminants, etc).

Compounds of the invention show particularly high activity against pestsin the order Lepidoptera (e.g. Alabama argillacea Hübner (cotton leafworm), Archips argyrospila Walker (fruit tree leaf roller), A. rosanaLinnaeus (European leaf roller) and other Archips species, Chilosuppressalis Walker (rice stem borer), Craphalocrosis medinalis Guenne(rice leaf roller), Crambus caliginosellus Clemens (corn root webworm),Crambus teterrellus Zincken (bluegrass webworm), Cydia pomonellaLinnaeus (codling moth), Earias insulana Boisduval (spiny bollworm),Earias vittella Fabricius (spotted bollworm), Helicoverpa armigeraHübner (American bollworm), Helicoverpa zea Boddie (corn earworm),Heliothis virescens Fabricius (tobacco budworm), Herpetogrammalicarsisalis Walker (sod webworm), Labesia botrana Denis &Schiffermüller (grape berry moth), Pectinophora gossypiella Saunders(pink bollworm), Phyllocnistis citrella Stainton (citrus leafminer),Pieris brassicae Linnaeus (large white butterfly), Pieris rapae Linnaeus(small white butterfly), Plutella xylostella Linnaeus (diamondbackmoth), Spodoptera exigua Hübner (beet armyworm), Spodotera lituraFabricius (tobacco cutworm, cluster caterpillar), Spodoptera frugiperdaJ. E. Smith (fall armyworm), Trichoplusia ni Hübner (cabbage looper) andTuta absoluta Meyrick (tomato leafminer)). Compounds of the inventionalso have commercially significant activity on members from the orderHomoptera including: Acyrthisiphon pisum Harris (pea aphid), Aphiscraccivora Koch (cowpea aphid), Aphis fabae Scopoli (black bean aphid),Aphis gossypii Glover (cotton aphid, melon aphid), Aphis pomi De Geer(apple aphid), Aphis spiraecola Patch (spirea aphid), Aulacorthum solaniKaltenbach (foxglove aphid), Chaetosiphon fragaefolii Cockerell(strawberry aphid), Diuraphis noxia Kurdjumov/Mordvilko (Russian wheataphid), Dysaphis plantaginea Paaserini (rosy apple aphid), Eriosomalanigerum Hausmann (wooly apple aphid), Hyalopterus pruni Geoffroy(mealy plum aphid), Lipaphis erysimi Kaltenbach (turnip aphid),Metpolophium dirrhodum Walker (cereal aphid), Macrosipum euphorblaeThomas (potato aphid), Myzus persicae Sulzer (peach-potato aphid, greenpeach aphid), Nasonovia ribisnigri Mosley (lettuce aphid), Pemphigusspp. (root aphids and gall aphids), Rhopalosiphum maidis Fitch (cornleaf aphid), Rhopalosiphum padi Linnaeus (bird cherry-oat aphid),Schizaphis graminum Rondani (greenbug), Sitobion avenae Fabricius(English grain aphid), Therioaphis maculata Buckton (spotted alfalfaaphid), Toxoptera aurantii Boyer de Fonscolombe (black citrus aphid),and Toxoptera citricada Kirkaldy (brown citrus aphid); Adelges spp.(adelgids); Phylloxera devastatrix Pergrand (pecan phylloxera); Bemisiatabaci Gennadius (tobacco whitefly, sweetpotato whitefly), Bemisiaargentifolii Bellows & Perring (silverleaf whitefly), Dialeurodes citriAshmead (citruc whitefly) and Trialeurodes vaporariorum Westwood(greenhouse whitefly); Empoasca fabae Harris (potato leafhopper),Laodelphax striatellus Fallen (smaller brown planthopper), Macrolestesquadrilineatus Forbes (aster leafhopper), Nephotettix cinticeps Uhler(green leafhopper), Nephotettix nigropictus Stãl (rice leafhopper),Nilaparvata lugens Stål (brown planthopper), Peregrinus maidis Ashmead(corn planthopper), Sogatella furcifera Horvath (white-backedplanthopper), Sogatodes orizicola Muir (rice delphacid), Typhlocybapomaria McAtee white apple leafhopper, Erythroneuora spp. (grapeleafhoppers); Magicidada septendecim Linnaeus (periodical cicada; Iceryapurchasi Maskell (cottony cushion scale), Quadraspidiotus perniciosusComstock (San Jose scale); Planococcus citri Risso (citrus mealybug);Pseudococcus spp. (other mealybug complex); Cacopsylla pyricola Foerster(pear psylla), Trioza diospyri Ashmead (persimmon psylla). Thesecompounds also have activity on members from the order Hemipteraincluding: Acrosternum hilare Say (green stink bug), Anasa tristis DeGeer (squash bug), Blissus leucopterus leucopterus Say (chinch bug),Corythuca gossypii Fabricius (cotton lace bug), Cryptopeltis modestaDistant (tomato bug), Dysdercus suturellus Herrich-Schäffer (cottonstainer), Euchistus servus Say (brown stink bug), Euchistus variolariusPalisot de Beauvois (one-spotted stink bug), Graptosthetus spp. (complesof seed bugs), Leptoglossus corculus Say (leaf-footed pine seed bug),Lygus lineolaris Palisot de Beauvois (tarnished plant bug), Nezaraviridula Linnaeus (southern green stink bug), Oebalus pugnax Fabricius(rice stink bug), Oncopeltus fasciatus Dallas (large milkweed bug),Pseudatomoscelis seriatus Reuter (cotton fleahopper). Other insectorders controlled by compounds of this invention include Thysanoptera(e.g., Frankliniella occidentalis Pergande (western flower thrip),Scirthothrips citri Moulton (citrus thrip), Sericothrips variabilisBeach (soybean thrip), and Thrips tabaci Lindeman (onion thrip); and theorder Coleoptera (e.g., Leptinotarsa decemlineata Say (Colorado potatobeetle, Epilachna varivestis Mulsant (Mexican bean beetle) and wirewormsof the genera Agriotes, Athous or Limonius).

Compounds of this invention can also be mixed with one or more otherbiologically active compounds or agents including insecticides,fungicides, nematocides, bactericides, acaricides, growth regulatorssuch as rooting stimulants, chemosterilants, semiochemicals, repellents,attractants, pheromones, feeding stimulants, other biologically activecompounds or entomopathogenic bacteria, virus or fungi to form amulti-component pesticide giving an even broader spectrum ofagricultural utility. Thus compositions of the present invention canfurther comprise a biologically effective amount of at least oneadditional biologically active compound or agent. Examples of suchbiologically active compounds or agents with which compounds of thisinvention can be formulated are: insecticides such as abamectin,acephate, acetamiprid, amidoflumet (S-1955), avermectin, azadirachtin,azinphos-methyl, bifenthrin, binfenazate, bufprofezin, carbofuran,chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl,chromafenozide, clothianidin, cyfluthrin, beta-cyfluthrin, cyhalothrin,lamda-cyhalothrin, cypermethrin, cyromazine, deltamethrin,diafenthiuron, diazinon, diflubenzuron, diemthoate, diofenolan,emamectin, endosulfan, esfenvalerate, ethiprole, fenothicarb,fenoxycarb, fenpropathrin, fenproximate, fenvalerate, fipronil,flonicamid, flucythrinate, tau-fluvalinate, flufenerim (UR-50701),flufenoxuron, fonophos, halofenozide, hexaflumuron, imidacloprid,indoxacarb, isofenphos, lufenuron, malathion, metaldehyde,methamidophos, methidathion, methomyl, methoprene, methoxychlor,monocrotophos, methoxyfenozide, niathiazin, novaluron, noviflumuron,(XDE-007), oxamyl, parathion, parathion-methyl, permethrin, phorate,phosalone, phosmet, phosphamidon, primicarb, profenofos, pymetrozine,pyridalyl, pyriproxyfen, rotenone, spinosad, spiromesifin (BSN 2060),sulprofos, tebufenozide, teflubenzuron, tefluthrin, terbufos,tetrachlorvinphos, thiacloprid, thiamethoxan, thiodicarb,thiosultap-sodium, tralomethrin, trichlorfon and triflumuron; fungicidessuch as acibenzolar, azoxystrobin, benomyl, blasticidin-S, Bordeauxmixture (tribasic copper sulfate), bromuconazole, carpropamid, captafol,captan, carbendazim, chloroneb, chlorothalonil, copper oxychloride,copper salts, cyflufenamid, cymoxanil, cyproconazole, cyprodinil,(S)-3,5-dichloro-N-(3-chloro-1-ethyl-1-methyl-2-oxopropyl)-4-methylbenzamide(RH 7281), diclocymet, (S-2900), diclomexine, dicloran, difenoconazole,(S)-3,5-dihydro-5-methyl-2-(methylthio)-5-phenyl-3-(phenylamino)-4H-imidazol-4-one(RP 407213), dimethomorph, dimoxystrobin, diniconazole, diniconazole-M,dodine, edifenphos, epoxiconazole, famoxadone, feamidone, fenarimol,fenbuconozaole, fencaramid (SZX0722), fenpiclonil, fenpropidin,fenpropimorph, fentin acetate, fentin hydroxide, fluazinam, fludioxonil,flumetover (RPA 403397), flumorf/flumorlin (SYP-L190), fluoxastrobin(HEC 5725), fluquinconazole, flusilazole, flutolanil, flutriafol, folpetfosetyl-aluminum, furalaxyl, furametpyr (S-82658), hexaconazole,ipconazole, iprobenfos, iprodione, isoprothiolane, kasugamycin,kresoxim-methyl, manocozeb, maneb, mefenoxam, mepronil, metalaxyl,metconazole, metominostrobin/fenominostrobin (SSF-126), metrafenone (AC375839), myclobutanil, neo-asozin (ferric methanearsonate), nicobifen,(BAS 510), orysastrobin, oxadixyl, penconazole, pencycuron, probenazole,prochloraz, propamocarb, propiconazole, proquinazid (DPX-KQ926),prothioconazole (JAU 6476), pyrifenox, pyraclostrobin, pyrimethanil,pyroquilon, quinoxyfen, spiroxamine, sulfur, tebuconazole,tetraconazole, thiabendazole, thifluzamide, thiophanate-methyl, thiram,tiadinil, triadimefon, triadimenol, tricyclazole, trifloxystrobin,triticonazole, validamycin and vinclozolin; nematocides such asaldicarb, oxamyl, fenamiphos, amitraz, chinomethionat, chlorobenzilate,cyhexatin, dicofol, dienchlor, etoxazole, fenazaquin, fenbutatin oxide,fenpropathrin, fenpyroximate, hexythiazox, propargite, pyridaben,tebufenpyrad; and biological agents such as Bacillus thuringiensisincluding ssp. aizawai and kurstaki, Bacillus thuringiensis deltaendotoxin, baculovirus, and entomophatogenic bacteria, virus and fungi.

A general reference for these agricultural protectants is The PesticideManual, 12th Edition, C. D. S. Tomlin, Ed., British Crop ProtectionCouncil, Farnham, Surrey, U.K., 2000.

Preferred insecticides and acaricides for mixing with compounds of thisinvention include pyrethroids such as cypermethrin, cyhalothrin,cyfluthrin and beta-cyfluthrin, esfenvalerate, fenvaleratea andtralomethrin; carbamates such as fenothicarb, methomyl, oxamyl andthiodicarb; neonicotinoids such as clothisanidin, imidacloprid andthiacloprid, neuronal sodium channel blockers such as indoxacarb,insecticidal macrocyclic lactones such as spinosad, abamectin,avermectin, and emamectin; γ-aminobutyric acid (GABA antagonists such asendosulfan, ethiprole and fipronil; insecticidal ureas such asflufenoxuron and triflumuron, juvenile hormone mimics such as diofenolanand pyriproxyfen; pymetrozine; and amitraz. Preferred biological agentsfor mixing with compoundso of this invention include Bacillusthuringiensis and Bacillus thuringiensis delta endotoxin as well asnaturally occuring and genetically modified viral insecticides includingmembers of the family Baculovirdiae as well as entomophagous fungi.

Most preferred mixtures include a mixture of a compound of thisinvention with cyhalothrin; a mixture of a compound of this inventionwith beta-cyfluthrin; a mixture of a compound of this invention withesfenvalerate; a mixture of a compound of this invention with methomyl;a mixture of a compound of this invention with imidacloprid; a mixtureof a compound of this invention with thiacloprid; a mixture of acompound of this invention with indoxacarb; a mixture of a compound ofthis invention with abamectin; a mixture of a compound of this inventionwith endosulfan; a mixture of a compound of this invention withethiprole; a mixture of a compound of this invention with fipronil; amixture of a compound of this invention with flufenoxuron; a mixture ofa compound of this invention with pyriproxyfen; a mixture of a compoundof this invention with pymetrozine; a mixture of a compound of thisinvention with amitraz; a mixture of a compound of this invention withBacillus thuringiensis and a mixture of a compound of this inventionwith Bacillus thuringiensis delta endotoxin.

In certain instances, combinations with other invertebrate pest controlcompounds or agents having a similar spectrum of control but a differentmode of action will be particularly advantageous for resistancemanagement. Thus, compositions of the present invention can furthercomprise an biologically effective amount of at least one additionalinvertebrate pest control compounds or agents having a similar spectrumof control but a different mode of action. Contacting a plantgenetically modified to express a plant protection compound (e.g.,protein) or the locus of the plant with a biologically effective amountof a compound of invention can also provide a broader spectrum of plantprotection and be advantageous for resistance management.

Invertebrate pests are controlled and protection of agronomoic,horticultrual and specialty crops, animal and human health is achievedby applying one or more of the compounds of this invention, in aneffective amount, to the environment of the pests including theagronomic and/or nonagronomic locus of the infestation, to the area tobe protected, or directly on the pests to be controlled. Thus, thepresent invention further comprises a method for the control of foliar-and soil-inhabiting invertebrates and protection of agronomic and/ornonagronomic crops, comprising contacting the invertebrates or theirenvironment with a biologically effective amount of one or more of thecompounds of the invention, or with a composition comprising at leastone such compound or a composition comprising at least one such compoundand an effective amount of at least one additional biologically activecompound or agent. A preferred method of contact is by spraying.Alternatively, a granular composition comprising a compound of theinvention can be applied to the plant foliage or the soil. Compounds ofthis invention are effective in delivery through plant uptake bycontacting the plant with a composition comprising a compound of thisinvention applied as a soil drench of a liquid formulation, a granularformulation to the soil, a nursery box treatment or a dip oftransplants. Other methods of contact include application of a compoundor a composition of the invention by direct and residual sprays, aerialsprays, seed coats, microencapsulations, systemic uptake, baits,eartags, boluses, foggers, fumigants, aerosols, dusts and many others.

The compounds of this invention can be incorporated into baits that areconsumed by the invertebrates or within devices such as traps and thelike. Granules or baits comprising between 0.01-5% active ingredient,0.05-10% moisture retaining agent(s) and 40-99% vegetable flour areeffective in controlling soil insects at very low application rates,particularly at doses of active ingredient that are lethal by ingestionrather than by direct contact.

The compounds of this invention can be applied in their pure state, butmost often application will be of a formulation comprising one or morecompounds with suitable carriers, diluents, and surfactants and possiblyin combination with a food depending on the contemplated end use. Apreferred method of application involves spraying a water dispersion orrefined oil solution of the compounds. Combinations with spray oils,spray oil concentrations, spreader stickers, adjuvants, other solvents,and synergists such as piperonyl butoxide often enhance compoundefficacy.

The rate of application required for elective control (i.e.“biologically effective amount”) will depend on such factors as thespecies of invertebrate to be controlled, the pest's life cycle, lifestage, its size, location, time of year, host crop or animal, feedingbehavior, mating behavior, ambient moisture, temperature, and the like.Under normal circumstances, application rates of about 0.01 to 2 kg ofactive ingredient per hectare are sufficient to control pests inagronomic ecosystems, but as little as 0.0001 kg/hectare may besufficient or as much as 8 kg/hectare may be required. For nonagronomicapplications, effective use rates will range from about 1.0 to 50mg/square meter but as little as 0.1 mg/square meter may be sufficientor as much as 150 mg/square meter may be required. One skilled in theart can easily determine the biologically effective amount necessary forthe desired level of invertebrate pest control.

The following Tests in the Biological Example of the Inventiondemonstrate the efficacy of methods of the invention for protectingplants from specific arthropod pests. “Control efficacy” representsinhibition of arthropod development (including mortality) that causessignificantly reduced feeding. The pest control protection afforded bythe compounds is not limited, however, to these species. See Index TableA for compound descriptions. The following abbreviations are used in theIndex Table which follows: t is tertiary, n is normal, i is iso, s issecondary, c is cyclo, Me is methyl, Et is ethyl, Pr is propyl and Bu isbutyl; accordingly i-Pr is isopropyl, s-Bu is secondary butyl, etc. Theabbreviation “Ex.” stands for “Example” and is followed by a numberindicating in which example the compound is prepared.

INDEX TABLE A

Compound R³ R² R⁴, R⁵ R⁶ R⁷ m.p. (° C.)  1 i-Pr H 2-Me CF₃ CH₃ 200-204 2 i-Pr H 2-Me CF₃ Et 123-126 (Ex. 1)  3 i-Pr H 2-Cl CF₃ CH₃ 233-235  4t-Bu H 2-Me CF₃ Et 215-218  5 i-Pr H 2-Me CH₃ Ph 238-239  6 i-Pr H 2-MeCH₃ CH₃ 206-208  7 i-Pr H 2-Me CH₃ CH₂CF₃ 246-248  8 i-Pr H 2-Cl Et CF₃235-237  9 i-Pr H 2-Me CH₃ CH₃, R⁸ is Cl 205-207  10 i-Pr H 2-Me CH₃4-CF₃—Ph 256-258  11 i-Pr H 2-Me CH₃ 2-CF₃—Ph 204-206  12 t-Bu H 2-MeCH₃ Ph 236-238  13 i-Pr H 2-F CH₃ Ph 227-229  14 i-Pr H 5-F CH₃ Ph209-211  15 i-Pr H 2-Cl CH₃ Ph 233-234  16 i-Pr H H CH₃ Ph 215-217  17i-Pr H 2-NO₂ CH₃ Ph 236-237  18 i-Pr H 2-Cl CF₃ Ph 240-242  19 i-Pr H2-Me CF₃ Ph 260-262 (Ex. 2)  20 i-Pr H 2-I CH₃ Ph 250-251  21 i-Pr H 2-ICH₃ 2-CF₃—Ph 251-253  22 H H 2-Me CH₃ Ph 253-255  23 Et Et 2-Me CH₃ Ph182-184  24 t-Bu H 2-Cl CF₃ Ph 232-234  25 i-Pr H 2-I CF₃ Ph 271-273  26t-Bu H 2-I CF₃ Ph 249-250  27 i-Pr H 2-Me CH₃ t-Bu 210-211  28 i-Pr H2-Br CF₃ Ph 257-259  29 i-Pr H 2-Br CH₃ Ph 246-247  30 i-Pr H 2-Me CF₃2-pyridinyl 237-238  31 i-Pr H 2,5-di-Cl CF₃ Ph >250  32 i-Pr, B is S H2-Me CF₃ Ph 169-172  33 i-Pr H 2-Me CF₃ 2-Cl—Ph 208-209  34 i-Pr H 2-ClCF₃ 2-Cl—Ph 234-235  35 i-Pr H 2-Me CF₃ 4-Cl—Ph 289-290  36 i-Pr H 2-ClCF₃ 4-Cl—Ph 276-278  37 i-Pr H 2-Cl CF₃ 2-pyridinyl 239-240  38 i-Pr H2-Me CF₃ 2-pyrimidinyl 205-208  39 i-Pr H 2-Me CF₃ 2-(3-CH₃-pyridinyl)183-187  40 i-Pr H 2-Me CF₂CF₃ Ph 231-232  41 i-Pr H 2-Cl CF₂CF₃ Ph206-207  42 t-Bu H 2-Cl CF₂CF₃ Ph 212-213  43 i-Pr H 2-Br CF₂CF₃ Ph219-222  44 i-Pr H 2-Me CF₃ 3-Cl—Ph 278-280  45 i-Pr H 2-Cl CF₃ 3-Cl—Ph272-273  46 i-Pr H 2-Me CF₃ 2-F—Ph 217-218  47 i-Pr H 2-Cl CF₃ 2-F—Ph220-221  48 i-Pr H 2-Me CF₃ 4-F—Ph 269-270  49 i-Pr H 2-Cl CF₃ 4-F—Ph279-280  52 i-Pr H 2-CF₃ CF₃ Ph 247-249  53 i-Pr H 2-Cl CF₃ i-Pr 255-258 54 i-Pr H 2-Me CF₃ 3-F—Ph 277-278  55 i-Pr H 2-Cl CF₃ 3-F—Ph 256-257 56 i-Pr H 2-Me CF₃ 2-CF₃—Ph 215-216  57 i-Pr H 2-Cl CF₃ 2-CF₃—Ph230-231  58 i-Pr H 2-Me CF₃ 2-Br—Ph 207-208  59 i-Pr H 2-Cl CF₃ 2-Br—Ph239-240  60 i-Pr H 2-OCH₃ CF₃ Ph 215-216  61 i-Pr H 5-Cl CF₃2-(3-CH₃-pyridinyl) 224-225  62 i-Pr H 5-Me CF₃ 2-(3-Cl-pyridinyl)179-181  63 s-Bu H 2-Cl CF₃ Ph >240  64 c-Pr H 2-Cl CF₃ Ph >240  65 Et H2-Cl CF₃ Ph >240  66 t-Bu H 2-CF₃ CF₃ Ph 230-233  67 Et H 2-CF₃ CF₃ Ph246-249  68 CH(CH₃)CH₂SCH₃ H 2-CF₃ CF₃ Ph 215-217  69 CH(CH₃)CH₂OCH₃ H2-CF₃ CF₃ Ph 220-223  70 i-Pr H 5-Cl CF₃ 2-(3-Cl-pyridinyl) 230-233  71i-Pr H 5-Me CF₃ 2-thiazolyl 201-203  72 i-Pr H 5-Me CF₃ 2-pyrazinyl252-253  73 i-Pr H 5-Me CF₃ 4-pyridinyl 224-228  74 i-Pr H 2-Me CF₃ i-Pr236-243  75 i-Pr H 2-Me CF₃ 2-CH₃—Ph 211-212  76 i-Pr H 2-Cl CF₃2-CH₃—Ph 232-234  77 i-Pr H 2-Br CF₃ 2-Cl—Ph 247-248  78 t-Bu H 2-Me CF₃2-Cl—Ph 216-217  79 i-Pr H 2-Me CF₃ 2-(3-CF₃-pyridinyl) 227-230 (Ex. 3) 80 CH₂CH₂Cl H 2-Cl CF₃ Ph 237-242  81 CH₂CH₂CH₂Cl H 2-Cl CF₃ Ph 233-239 82 CH(CH₃)CO₂CH₃ H 2-Cl CF₃ Ph 221-222  83 CH(i-Pr)CO₂CH₃ H 2-Cl CF₃ Ph212-213 (S configuration)  84 i-Pr H 2-Me CF₃ 2,6-di-Cl—Ph 267-268  85i-Pr H 2-Cl CF₃ 2,6-di-Cl—Ph 286-287  86 i-Pr H 2-Me Br Ph 253-255  87i-Pr H 2-Cl Br Ph 247-248  88 i-Pr H 2-Me CF₃ i-Bu 205-210  89 i-Pr H2-Me CF₃ CH₂Ph 235-237  90 i-Pr H 2-Me CF₃ 2-(3-CH₃O-pyridinyl) 221-222 91 i-Pr H 2-Me CF₃ 3-pyridinyl 260-261  92 i-Pr H 2-Me CF₃4-quinolinyl >260  93 i-Pr H 2-Me CN 2-(3-Cl-pyridinyl) 203-204  94 i-PrH 2-Me CF₃ 2,4-di-F—Ph 245-246  95 i-Pr H 2-Cl CF₃ 2,4-di-F—Ph 252-253 96 i-Pr H 2-Me CF₃ 2-Et—Ph 207-209  97 i-Pr H 2-Cl CF₃ 2-Et—Ph 221-222 98 i-Pr H H CF₃ 2-Cl—Ph 206-207  99 t-Bu H H CF₃ 2-Cl—Ph 197-198 100CH(CH₃)CH₂OCH₃ H H CF₃ 2-Cl—Ph 145-148 101 CH(CH₃)CH₂SCH₃ H H CF₃2-Cl—Ph 158-160 102 CH(CH₃)CH₂SCH₃ H 2-Cl CF₃ Ph 184-186 103CH(CH₃)CH₂OCH₃ H 2-Cl CF₃ Ph 217-218 104 n-Pr H 2-Cl CF₃ Ph 247-248 105i-Bu H 2-Cl CF₃ Ph 244-245 106 CH₃ H 2-Cl CF₃ Ph >250 107 i-Pr Me 2-ClCF₃ Ph 193-194 108 CH₂C≡CH H 2-Cl CF₃ Ph >250 109 CH₂CH═CH₂ H 2-Cl CF₃Ph 248-249 110 CH₂(2-furanyl) H 2-Cl CF₃ Ph 246-247 113 i-Pr H 2-Me CF₃4-(3,5-di-Cl-pyridinyl) 239-242 114 i-Pr H 2-Cl CF₃4-(3,5-di-Cl-pyridinyl) 229-231 115 CH(CH₃)CH₂SCH₃ H 2-Me CF₃ 2-Cl—Ph194-195 116 CH(CH₃)CH₂OCH₃ H 2-Me CF₃ 2-Cl—Ph 181-183 117 s-Bu H 2-MeCF₃ 2-Cl—Ph 199-200 118 c-Pr H 2-Me CF₃ 2-Cl—Ph 234-235 119 n-Pr H 2-MeCF₃ 2-Cl—Ph 222-223 120 i-Bu H 2-Me CF₃ 2-Cl—Ph 235-237 121 Me H 2-MeCF₃ 2-Cl—Ph 242-243 122 i-Pr Me 2-Me CF₃ 2-Cl—Ph 90-93 123 CH₂C≡CH H2-Me CF₃ 2-Cl—Ph 215-216 124 Et H 2-Me CF₃ 2-Cl—Ph 228-229 125 CH₂CH═CH₂H 2-Me CF₃ 2-Cl—Ph 227-228 126 CH₂(2-furanyl) H 2-Me CF₃ 2-Cl—Ph 218-219127 CH(CH₃)CH₂SCH₃ H 2-Me CF₃ Ph 179-180 128 CH(CH₃)CH₂OCH₃ H 2-Me CF₃Ph 219-220 129 s-Bu H 2-Me CF₃ Ph 244-245 130 c-Pr H 2-Me CF₃ Ph >250131 n-Pr H 2-Me CF₃ Ph 238-239 132 i-Bu H 2-Me CF₃ Ph 237-238 133 Me H2-Me CF₃ Ph 263-265 134 i-Pr Me 2-Me CF₃ Ph 178-179 135 CH₂C≡CH H 2-MeCF₃ Ph 253-254 136 Et H 2-Me CF₃ Ph 244-245 137 CH₂CH═CH₂ H 2-Me CF₃ Ph240-241 138 CH₂(2-furanyl) H 2-Me CF₃ Ph 245-246 139 i-Pr H 2-OCHF₂ CF₃2-Cl—Ph 200-201 140 i-Pr H 2-OCH₃ CF₃ 2-Cl—Ph 206-207 141 i-Pr H 2-I CF₃2-Cl—Ph 253-256 142 i-Pr H 2-Me Br 2-Cl—Ph 147-150 143 i-Pr H 2-Cl Br2-Cl—Ph 246-247 144 i-Pr H 2-Me CF₃ 2-CH₃O—Ph 218-219 145 i-Pr H 2-ClCF₃ 2-CH₃O—Ph 243-244 146 i-Pr H 2-Me CF₃ 1-isoquinolinyl 252-253 147CH(CH₃)CH₂SCH₃ H 2-Cl CF₃ 2-Cl—Ph 217-218 148 CH(CH₃)CH₂OCH₃ H 2-Cl CF₃2-Cl—Ph 207-208 149 s-Bu H 2-Cl CF₃ 2-Cl—Ph 216-217 150 c-Pr H 2-Cl CF₃2-Cl—Ph 261-262 151 n-Pr H 2-Cl CF₃ 2-Cl—Ph 231-232 152 i-Bu H 2-Cl CF₃2-Cl—Ph 255-256 153 Me H 2-Cl CF₃ 2-Cl—Ph 233-235 154 i-Pr Me 2-Cl CF₃2-Cl—Ph 127-128 155 CH₂C≡CH H 2-Cl CF₃ 2-Cl—Ph 226-227 156 Et H 2-Cl CF₃2-Cl—Ph 244-246 157 CH₂CH═CH₂ H 2-Cl CF₃ 2-Cl—Ph 235-236 158CH₂(2-furanyl) H 2-Cl CF₃ 2-Cl—Ph 207-208 160 i-Pr H C≡CH CF₃ 2-Cl—Ph228-230 161 i-Pr H 2-Cl C≡CH 2-Cl—Ph 219-222 162 i-Pr H 2-Me H H, R⁸ isCH₃ 220-223 163 i-Pr H 2-Me CH₃ Ph, R⁸ is Cl 209-210 164 i-Pr, B is S H2-Cl CF₃ Ph 169-174 165 i-Pr H 2-Me CF₃ 2,6-di-F—Ph 223-225 166 i-Pr H2-Me CF₃ 2-Cl-6-F—Ph 203-206 167 i-Pr H 2-Cl CF₃ 2-Cl-6-F—Ph 218-221 168i-Pr H 2-Me-4-Br CF₃ 2-F—Ph 232-233 169 t-Bu H 2-Cl CF₃2-(3-Cl-pyridinyl) 250-251 170

H 2-Cl CF₃ 2-(3-Cl-pyridinyl) >250 171 Et Et 2-Cl CF₃ 2-Cl—Ph 252-253172 Me Me 2-Cl CF₃ 2-Cl—Ph 234-235 173 Et Et 2-Me CF₃ 2-Cl—Ph 237-238174 Me Me 2-Me CF₃ 2-Cl—Ph 225-226 176 i-Pr H 2-Cl CF₃ 2-pyrazinyl242-243 177 t-Bu H 2-Me-4-Br CF₃ 2-Cl—Ph >260 178 CH(CH₃)CH₂OCH₃ H 2-MeCF₃ 2-(3-Cl-pyridinyl) 176-177 179 CH(CH₃)CH₂SCH₃ H 2-Me CF₃2-(3-Cl-pyridinyl) 196-197 180 CH(CH₃)CH₂OCH₃ H 2-Cl CF₃2-(3-Cl-pyridinyl) 197-198 181 CH(CH₃)CH₂SCH₃ H 2-Cl CF₃2-(3-Cl-pyridinyl) 202-203 182 i-Pr H 2-Me CF₃ 2-I—Ph 221-222 183 i-Pr H2-Cl CF₃ 2-I—Ph 238-240 184 i-Pr H 2-Me CF₃ 2-(HC≡C)—Ph 215-217 185 i-PrH 2-Cl CF₃ 2-(HC≡C)—Ph 244-246 186 i-Pr H 2-Me CF₃ 2-Cl-4-F—Ph 203-205187 i-Pr H 2-Cl CF₃ 2-Cl-4-F—Ph 218-219 188 Et Et 2-Me CF₃ 2-Cl—Ph243-247 189 i-Pr H 2-Me CF₃ 2,6-di-Me—Ph 259-260 190 i-Pr H 2-Cl CF₃2,6-di-Me—Ph 268-269 191 i-Pr H 2-Me CF₃ 2,6-di-Cl-4-CN—Ph * 192 i-Pr H2-Me CF₃ 2-CN—Ph 225-235 193 i-Pr H 2-Me CF₃ 2-(CF₃O)—Ph 214-215 194i-Pr H 2-Cl CF₃ 2-(CF₃O)—Ph 223-224 195 i-Pr H 2-Me CF₃ 2-Br-4-F—Ph202-203 196 i-Pr H 2-Cl CF₃ 2-Br-4-F—Ph 222-223 197 i-Pr H 2-Me CF₃2-(3-Me-pyrazinyl) 205-207 198 Me H 2-Cl CF₃ 2-(3-Cl-pyridinyl) 215-220199 CH₂C≡CH H 2-Cl CF₃ 2-(3-Cl-pyridinyl) 197-198 200 Me H 2-Me CF₃2-(3-Cl-pyridinyl) 193-196 201 Et H 2-Me CF₃ 2-(3-Cl-pyridinyl) 204-206202 CH₂C≡CH H 2-Me CF₃ 2-(3-Cl-pyridinyl) 177-178 203 i-Pr H 2-Me CF₃4-(8-Cl-quinolinyl) >250 204 i-Pr H 2-Me CF₃ 4-(2-Me-quinolinyl) >250205 i-Pr H 2-Cl CF₃ 4-(2-Me-quinolinyl) >250 206 i-Pr H 2-Me CF₃4-(7-Cl-quinolinyl) >250 207 i-Pr H 2,4-Br₂ CF₃ 2-Cl—Ph 233-234 208 i-PrH 2-Br Br 2-Cl—Ph 255-258 209 Me H 2-Me Br 2-Cl—Ph 236-237 210 t-Bu H2-Cl Br 2-Cl—Ph 260-261 211 Et H 2-Me Br 2-Cl—Ph 254-255 212 t-Bu H 2-MeBr 2-Cl—Ph 259-260 213 c-Bu H 2-Cl CN 2-(3-Cl-pyridinyl) 177-180 214i-Pr H 2-Me CF₃ 2-(3-Cl-pyridinyl) 237-239 (Ex. 4, 5) 215 i-Pr H 2-MeCF₃ 4-(6-Cl-quinolinyl) >250 216 Me Me 2-Me CF₃ 4-(6-Cl-quinolinyl) >250218 i-Pr H 2-Cl CN 2-(3-Cl-pyridinyl) 195-200 219 t-Bu H 2-Cl CN2-(3-Cl-pyridinyl) >250 220 Et H 2-Cl CN 2-(3-Cl-pyridinyl) 200-205 221i-Pr H 2-Cl CF₃ 2-(3-Me-pyrazinyl) 225-230 222 t-Bu H 2-Cl CF₃2-(3-Me-pyrazinyl) 235-240 223 Et H 2-Cl CF₃ 2-(3-Me-pyrazinyl) 210-220224 i-Pr H 2-Me CF₃ 3-(2-Cl-pyridinyl) * 225 i-Pr H 2-Cl CF₃2,3-di-Cl—Ph 217-219 226 t-Bu H 2-Cl CF₃ 2,3-di-Cl—Ph 254-256 227 i-Pr H2-Me CF₃ 2,3-di-Cl—Ph 208-209 228 t-Bu H 2-Me CF₃ 2,3-di-Cl—Ph 232-233229 t-Bu H 2-Me-4-Br Br 2-Cl—Ph 239-241 230 Me H 2-Me-4-Br Br 2-Cl—Ph150-152 231 Et H 2-Me-4-Br Br 2-Cl—Ph 223-225 232 i-Pr H 2-Me-4-Br Br2-Cl—Ph 197-198 233 Me H 2-Me CF₃ 2-F—Ph 245-247 234 CH₂C≡CH H 2-Me CF₃2-F—Ph 222-227 235 Me Me 2-Cl CF₃ 2-Cl—Ph 234-236 236 CH₂C≡CH H2-Me-4-Br Br 2-Cl—Ph 187-188 237 i-Pr H 2-Cl CF₃ 2-(3-Me-pyridinyl)224-225 238 i-Pr H 2-Cl CF₃ 2-(3-Cl-pyridinyl) 230-233 239 i-Pr H 2-MeCF₃ 2-pyrazinyl 252-253 240 i-Pr H 2-Me CF₃ 2-thiazolyl 201-203 241 i-PrH 2-Me CF₃ 4-pyridinyl 224-228 242 i-Pr H 2-Me CF₃ 2-(3-Cl-pyridinyl)249-250 243 i-Pr H 2-Me CF₃ Ph, R⁸ is CH₃ 246-248 244 Me Me 2-Me CF₃2-Cl—Ph 234-235 245 i-Pr H 2-Me CF₃ CH═CHCH₃ 225-228 246 i-Pr H 2-Me CF₃2-Cl-6-Me—Ph 247 i-Pr H 2-Cl CF₃ 2-Cl-6-Me—Ph 248 i-Pr H 2-Cl CF₃4-CN—Ph * 249 i-Pr H 2-Cl CF₃ 2,6-di-Cl-4-CN—Ph * 250 i-Pr H 2-Cl CF₃2-Cl-4-CN—Ph * 251 i-Pr H 2-Cl CN Ph * 252 i-Pr H 2-Me CF₃ 4-CN—Ph271-272 253 i-Pr H 2-Me CF₃ 3-CN—Ph 263-264 254 i-Pr H 2-Me CF₃2-Cl-4-CN—Ph * 255 i-Pr H 2-Me CN Ph * 256 i-Pr H 2-Cl CF₃ 3-CN—Ph * 257i-Pr H 2-Me CF₃ 2-Me-4-F—Ph 204-206 258 i-Pr H 2-Cl CF₃ 2-Me-4-F—Ph212-213 259 i-Pr H 2-Me CF₃ 2,4-di-Me—Ph 189-190 260 t-Bu H 2-Me CF₃2,4-di-Me—Ph 197-198 261 t-Bu H 2-Cl CF₃ 2,4-di-Me—Ph 234-235 262 i-Pr H2-Me CF₃ n-Bu, R⁸ is Cl 95-98 263 Me H 2-Cl CF₃ 4-(7-Cl-quinolinyl) >250264 Et H 2-Cl CF₃ 4-(7-Cl-quinolinyl) >250 265 CH₂CH═CH₂ H 2-Cl CF₃4-(7-Cl-quinolinyl) >250 266 i-Pr H 2-Cl CF₃ 4-(8-Cl-quinolinyl) >250267 i-Pr H 2-Me CF₃ 2-(3-CN-pyridinyl) 237-239 268 i-Pr H 2-Me CF₃1-(6-Cl-isoquinolinyl) >250 269 t-Bu H 2-Me CF₃ 1-(6-Cl-isoquinolinyl)227-229 270 Me Me 2-Me CF₃ 1-(6-Cl-isoquinolinyl) >250 271 i-Pr H 2-MeCF₃ 2-Cl-4-CN-6-Me—Ph * 272 i-Pr H 2-Me-4-Br Br 2-Cl—Ph 187-188 273CH₂CH(OCH₃)₂ H 2-Me CF₃ 2-Cl—Ph 205-207 274 CH₂CH(OCH₃)₂ Me 2-Me CF₃2-Cl—Ph 185-190 275 CH₂CH₂CH(OCH₃)₂ H 2-Me CF₃ 2-Cl—Ph 85-90 276 Me H2-Me CF₃ 2,6-di-Cl—Ph 280-282 277 Et H 2-Me CF₃ 2,6-di-Cl—Ph 274-275 278t-Bu H 2-Me CF₃ 2,6-di-Cl—Ph 285-286 279 t-Bu H 2-Cl CF₃ 2,6-di-Cl—Ph290-291 280 i-Pr H 2-Me H 2-Cl—Ph * 281 i-Pr H 2-Me H 2-Me—Ph * 282 i-PrH 2-Me H 2-F—Ph * 283 i-Pr H 2-Me Br 2-(3-Cl-pyridinyl) 206-209 284CH₂CH₂CN H 2-Me CF₃ 2-Cl—Ph 189-195 285 i-Pr H 2-Me CN 2-Cl—Ph * 286i-Pr H 2-Me CF₃ 2-(3-CH₃O-pyrazinyl) 195-200 287 i-Pr H 2-Me Br2,6-di-Cl—Ph 265-267 288 t-Bu H 2-Me Br 2,6-di-Cl—Ph 282-284 289 i-Pr H2-Cl Br 2,6-di-Cl—Ph 277-279 290 t-Bu H 2-Cl Br 2,6-di-Cl—Ph 296-298 291i-Pr H 2-Me Br 2-Cl-4-F—Ph 236-238 292 t-Bu H 2-Me Br 2-Cl-4-F—Ph249-250 293 i-Pr H 2-Cl Br 2-Cl-4-F 176-177 294 t-Bu H 2-Cl Br2-Cl-4-F—Ph 257-258 295 i-Pr H 2-I Br 2-Cl-4-F 227-229 296 c-Bu H 2-ClCF₃ 2-(3-Cl-pyridinyl) 230-231 297 i-Pr H 2-Cl Br 2-(3-Cl-pyridinyl)231-234 298 t-Bu H 2-Cl Br 2-(3-Cl-pyridinyl) 245-248 299 Et H 2-Cl Br2-(3-Cl-pyridinyl) 219-222 300 Et H 2-Me Br 2-(3-Cl-pyridinyl) 217-220301 t-Bu H 2-Me Br 2-(3-Cl-pyridinyl) 237-240 302 CH₂CN H 2-Me Br2-(3-Cl-pyridinyl) 227-229 303 t-Bu H 2-Me CN 2-(3-Cl-pyridinyl) 215-225304 c-Bu H 2-Me CN 2-(3-Cl-pyridinyl) 105-115 305 c-Bu H 2-Me CF₃2-(3-Cl-pyridinyl) 187-190 306 c-pentyl H 2-Me CF₃ 2-(3-Cl-pyridinyl)190-195 307 s-Bu H 2-Me CF₃ 2-(3-Cl-pyridinyl) 170-180 308 c-pentyl H2-Cl CF₃ 2-(3-Cl-pyridinyl) 215-222 309 s-Bu H 2-Cl CF₃2-(3-Cl-pyridinyl) 210-220 313 i-Pr H 2-Me Cl 2-(3-Cl-pyridinyl) 204-206314 t-Bu H 2-Me Cl 2-(3-Cl-pyridinyl) 210-213 315 t-Bu H 2-Cl Cl2-(3-Cl-pyridinyl) 237-239 316 i-Pr H 2-Cl Cl 2-(3-Cl-pyridinyl) 159-162317 CH(CH₃)₂CH₂CH₃ H 2-Me CN 2-(3-Cl-pyridinyl) 165-175 318 c-hexyl H2-Cl CF₃ 2-(3-Cl-pyridinyl) 250-260 319 CH(CH₃)₂CH₂CH₃ H 2-Cl CF₃2-(3-Cl-pyridinyl) 200-210 320 i-Pr H 2,4-di-Me CF₃ 2-Cl—Ph 239-240 321i-Pr H 2-Me CF₃ 2-Cl-5-CN—Ph * 322 i-Pr H 2-Me H 2-(3-Cl-pyridinyl)111-115 323 i-Pr H 2-Me CF₃ 2-CO₂Me—Ph 324 i-Pr H 2-Me-4-Br CF₃2,6-di-Cl—Ph 230-233 325 t-Bu H 2-Me-4-Br CF₃ 2,6-di-Cl—Ph >250 326 Me H2-Me-4-Br CF₃ 2,6-di-Cl—Ph 228-230 327 CH₂CN H 2-Me-4-Br CF₃2,6-di-Cl—Ph 228-230 328 i-Pr H 2,4-di-Cl CF3 2-Cl—Ph 223-224 329 i-Pr H2-Me CF₃ 2-Cl-4-CF₃-6-Cl—Ph 206-207 330 i-Pr H 2-Me CF₃5-(1,3-di-Me-4-Cl-pyrazolyl) 231-232 331 i-Pr H 2-Me CF₃2-(4,6-di-Me-pyrimidinyl) 220-222 332 i-Pr H 2-Cl CF₃2-(4,6-di-Me-pyrimidinyl) 152-154 333 t-Bu H 2-Me CF₃2-(4,6-di-Me-pyrimidinyl) 124-127 334 t-Bu H 2-Cl CF₃2-(4,6-di-Me-pyrimidinyl) 179-182 335 i-Pr H 4-I CF₃ 2-Cl—Ph 218-219 336i-Pr H 2-Me-4-OCH₃ CF₃ 2-(3-Cl-pyridinyl) 187-188 337 i-Pr H 2-Me CF₃2-F-4-Cl-5-(i-PrO)—Ph 214-216 338 CH₂CN H 2-Me Cl 2-(3-Cl-pyridinyl)190-195 339 Et H 2-Cl CF₃ 2-(3-Cl-pyridinyl) 217-219 340 i-Pr H2-Me-4-Br CF₃ 2,3-di-Cl—Ph >250 341 i-Pr H 2-Me CF₃ 2,5-di-Cl—Ph >250342 i-Pr H 2-Cl-4-Br CF₃ 2,3-di-Cl—Ph 251-253 343 CH₂CN H 2-Cl CF₃2,3-di-Cl—Ph 185-190 344 CH₂CH₂SCH₂CH₃ H 2-Me CF₃ 2-(3-Cl-pyridinyl)197-200 345 CH₂CH₂CH₂SCH₃ H 2-Me CF₃ 2-(3-Cl-pyridinyl) 185-190 346CH₃(2-furanyl) H 2-Me CF₃ 2-(3-Cl-pyridinyl) 210-215 347 CH₂C(═CH₂)CH₃ H2-Me CF₃ 2-(3-Cl-pyridinyl) 225-229 348 CH₂CH₂OCH₃ H 2-Me CF₃2-(3-Cl-pyridinyl) 215-218 349 CH₂CH₂CH₂OH H 2-Me CF₃ 2-(3-Cl-pyridinyl)210-212 350 CH₂CH₂Cl H 2-Me CF₃ 2-(3-Cl-pyridinyl) 206-216 351 CH₂CH₂OHH 2-Me CF₃ 2-(3-Cl-pyridinyl) 217-220 352 CH(CH₃)CH₂OH H 2-Me CF₃2-(3-Cl-pyridinyl) 110-115 353 CH₂CH(Br)CH₂Br H 2-Me CF₃2-(3-Cl-pyridinyl) 217-220 354 CH₂CO₂CH₃ H 2-Me CF₃2-(3-Cl-pyridinyl) >250 355 CH₂CH(OH)CH₂OH H 2-Me CF₃2-(3-Cl-pyridinyl) >250 356 CH₂CH₂CH₂Cl H 2-Me CF₃ 2-(3-Cl-pyridinyl)207-212 357 CH(CH₂OH)CH₂CH₃ H 2-Me CF₃ 2-(3-Cl-pyridinyl) 173-176 358i-Pr H 2-Me CF₃ 2-(5-CF₃-pyridinyl) 270-275 359 Et H 2-Me CF₃2-(3,6-di-Me-pyrazinyl) 210-215 360 i-Pr H 2-Me CF₃2-(3,6-di-Me-pyrazinyl) 215-220 361 t-Bu H 2-Me CF₃2-(3,6-di-Me-pyrazinyl) 265-270 362 Et H 2-Cl CF₃2-(3,6-di-Me-pyrazinyl) 214-217 363 i-Pr H 2-Cl CF₃2-(3,6-di-Me-pyrazinyl) 215-218 364 i-Pr H 2-Me OCH₃ 2-Cl—Ph 137-140 365i-Pr H 2-Cl OCH₃ 2-Cl—Ph 155-158 366 i-Pr H 2-Me Me 2-Cl—Ph 151-154 367i-Pr H 2-Cl Me 2,6-di-Cl—Ph 242-244 368 CH₂CH(OH)CH₃ H 2-Me CF₃2-(3-Cl-pyridinyl) 123-125 369 CH₂CH(OH)CH₂CH₃ H 2-Me CF₃2-(3-Cl-pyridinyl) 175-180 370 CH₂CN H 2,4-di-Br CF₃ 2-(3-Cl-pyridinyl)142-143 371 c-Pr H 2,4-di-Br CF₃ 2-(3-Cl-pyridinyl) 213-214 372 CH₂CN H2,4-di-Cl CF₃ 2-(3-Cl-pyridinyl) 201-202 373 i-Pr H 2,6-di-Me CF₃2-(3-Cl-pyridinyl) 204-205 374 t-Bu H 2,6-di-Me CF₃ 2-(3-Cl-pyridinyl)242-243 375 t-Bu H 2-Me CF₃ 2-(5-CF₃-pyridinyl) 220-230 376 C(CH₃)₂CH₂OHH 2-Me CF₃ 2-(3-Cl-pyridinyl) 205-210 377 CH₂CH₂F H 2-Me CF₃2-(3-Cl-pyridinyl) 127-130 378 i-Pr H 2-Me CF₃ 2-(4-Me-pyrimidinyl)196-197 379 i-Pr H 2-Cl CF₃ 2-(4-Me-pyrimidinyl) 208-210 380 t-Bu H 2-MeCF₃ 2-(4-Me-pyrimidinyl) 180-182 381 t-Bu H 2-Cl CF₃2-(4-Me-pyrimidinyl) 182-184 382 s-Bu H 2-Me CF₃ 2-(3-Et-pyrazinyl)160-165 383 Et H 2-Me CF₃ 2-(3-Et-pyrazinyl) 185-190 384 i-Pr H 2-Me CF₃2-(3-Et-pyrazinyl) 180-183 385 CH₂CF₂CF₃ H 2-Cl CF₃ 2-Cl—Ph 258-260 386t-Bu H 2-Me CF₃ 2-(3-Et-pyrazinyl) 180-185 387 CH₂CF₃ H 2-Cl CF₃ 2-Cl—Ph262-264 388 CH₂CN H 2-Me-4-Br CF₃ 2-(3-Cl-pyridinyl) 192-193 389CH(CH₃)CH₂OH H 2-Me CF₃ 2-Cl—Ph 203-205 390 i-Pr H 2-Me Cl 2-Cl—Ph207-209 391 i-Pr H 2-Cl Cl 2-Cl—Ph 236-237 392 i-Pr H 2-Me I 2-Cl—Ph225-226 393 i-Pr H 2-Cl I 2-Cl—Ph 251-253 394 CH(CH₃)CH₂Cl H 2-Me CF₃2-Cl—Ph 212-214 395 H H 2-Me CF₃ 2-(3-Cl-pyridinyl) 217-220 396 i-Pr H2-Cl CF₃ 4-(5,6-di-Me-pyrimidinyl) 218-220 397 t-Bu H 2-Cl CF₃4-(5,6-di-Me-pyrimidinyl) 212-214 398 i-Pr H 2-Cl CF₃4-(2,5,6-tri-Me-pyrimidinyl) 162-164 399 i-Pr H 2-Me CF₃4-(5,6-di-Me-pyrimidinyl) 162-164 400 CH₂CH(OH)CH₃ H 2-Me CF₃ 2-Cl—Ph207-209 401 H H 2-Me CF₃ 2-Cl—Ph 230-232 402 CH₂CH(Cl)CH₃ H 2-Me CF₃2-Cl—Ph 230-232 403 CH₂CH₂CN H 2-Cl CF₃ 2-(3-Cl-pyridinyl) 215-217 404CH₂CH₂F H 2-Cl CF₃ 2-(3-Cl-pyridinyl) 212-214 405 CH₂CH₂CN H 2-Cl CF₃2-Cl—Ph * 406 i-Pr H 2-Me-4-Br CN 2-(3-Cl-pyridinyl) * 407 CH₂CN H2-Me-4-CF₃ CF₃ 2-(3-Cl-pyridinyl) 211-213 408 i-Pr H 2-Me CF32,5-di-F—Ph 179-181 409 i-Pr H 2,4-di-Br CN 2-(3-Cl-pyridinyl) * 410t-Bu H 2,4-di-Br CN 2-(3-Cl-pyridinyl) 145-147 411 Me H 2,4-di-Br CN2-(3-Cl-pyridinyl) 165-168 412 Et H 2,4-di-Br CN 2-(3-Cl-pyridinyl)179-181 413 Me H 2-Me-4-Br Me 2-(3-Cl-pyridinyl) 141-143 414 t-Bu H2-Me-4-Br Me 2-(3-Cl-pyridinyl) 161-163 415 i-Pr H 2-Me-4-Br Me2-(3-Cl-pyridinyl) 141-143 416 Et H 2-Me-4-Br Me 2-(3-Cl-pyridinyl)161-163 417 i-Pr H 2-Me Me 2-(3-Cl-pyridinyl) 193-195 418 Me H 2-Me Me2-(3-Cl-pyridinyl) 194-196 419 i-Pr H 2-Me-4-Cl CN 2-(3-Cl-pyridinyl)188-190 420 t-Bu H 2-Me-4-Cl CN 2-(3-Cl-pyridinyl) 148-151 421 Me H2-Me-4-Cl CN 2-(3-Cl-pyridinyl) 182-184 422 Me H 2-Me Br2-(3-Cl-pyridinyl) 210-212 423 H H 2-Cl CF₃ 2-Cl—Ph 203-205 424 H H2-Me-4-Br CF₃ 2-(3-Cl-pyridinyl) 243-245 425 t-Bu H 2-Me CF₃5-(1,3-di-Me-4-Cl-pyrazolyl) 220-221 426 i-Pr H 2-Cl CF₃5-(1,3-di-Me-4-Cl-pyrazolyl) 264-266 427 t-Bu H 2-Cl CF₃5-(1,3-di-Me-4-Cl-pyrazolyl) 231-232 428 CH₂CN H 2-Br-4-Me CF₃2-(3-Cl-pyridinyl) 149-150 429 i-Pr H 2-Me-4-Cl Cl 2-Cl—Ph 180-181 430i-Pr H 2-Me-4-Br Br 2,6-di-Cl—Ph 238-239 431 i-Pr H 2-Cl-4-Me CF₃2-(3-Cl-pyridinyl) 170-171 432 t-Bu H 2-Cl-4-Me CF₃ 2-(3-Cl-pyridinyl)167-169 433 Me H 2-Cl-4-Me CF₃ 2-(3-Cl-pyridinyl) 162-164 434 H H2-Me-4-Br Br 2-(3-Cl-pyridinyl) 235-237 435 Me H 5-Cl CF₃2-(3-Cl-pyridinyl) 207-208 436 CH₂CN H 5-Cl CF₃ 2-(3-Cl-pyridinyl)178-179 437 Me H 5-Me CF₃ 2-(3-Cl-pyridinyl) 166-167 438 CH₂CN H 5-MeCF₃ 2-(3-Cl-pyridinyl) 191-192 439 H H 2-Me-4-Br CF₃ 2-(3-Cl-pyridinyl)243-244 440 i-Pr H 2-Me CF₃ 4-pyrimidinyl 441 i-Pr H 2-Cl CF₃4-pyrimidinyl 442 t-Bu H 2-Me CF₃ 4-pyrimidinyl 443 t-Bu H 2-Cl CF₃4-pyrimidinyl 444 i-Pr H 2,3-di-Me CF₃ 2-(3-Cl-pyridinyl) 173-175 445t-Bu H 2,3-di-Me CF₃ 2-(3-Cl-pyridinyl) 149-150 446 Me H 2,3-di-Me CF₃2-(3-Cl-pyridinyl) 164-166 447 H H 2,3-di-Me CF₃ 2-(3-Cl-pyridinyl)201-203 448 H H 2-Cl-4-Br CF₃ 2-(3-Cl-pyridinyl) 240-242 449 H H2-Cl-4-Me CF₃ 2-(3-Cl-pyridinyl) 223-225 450 i-Pr H 2-Me CF₃4-(5-Cl-pyrimidinyl) 451 t-Bu H 2-Me CF₃ 4-(5-Cl-pyrimidinyl) 452 t-Bu H2-Cl CF₃ 4-(5-Cl-pyrimidinyl) 453 c-Pr H 2-Cl CF₃ 2-(3-Cl-pyridinyl)224-228 454 CH₂CN H 2-Me-4-Br Br 2-(3-Cl-pyridinyl) 232-234 455 CH₂CN H2-Me-4-I CF₃ 2-(3-Cl-pyridinyl) 221-222 456 Me H 2,4-di-Cl CF₃ 2-Cl—Ph232-233 457 Et H 2,4-di-Cl CF₃ 2-Cl—Ph 247-248 458 t-Bu H 2,4-di-Cl CF₃2-Cl—Ph 223-224 459 CH₂CN H 2,4-di-Cl CF₃ 2-Cl—Ph 229-231 460 i-Pr H2-Me CF₃ 5-(1-Me-pyrazolyl) 240-241 461 t-Bu H 2-Me CF₃5-(1-Me-pyrazolyl) 233-234 462 i-Pr H 2-Cl CF₃ 5-(1-Me-pyrazolyl)247-248 463 t-Bu H 2-Cl CF₃ 5-(1-Me-pyrazolyl) 262-263 464 i-Pr H 2-MeCF₃ 4-(2,6-di-Me-5-Cl-pyrimidinyl) 465 i-Pr H 2-Cl CF₃4-(2,6-di-Me-5-Cl-pyrimidinyl) 466 t-Bu H 2-Me CF₃4-(2,6-di-Me-5-Cl-pyrimidinyl) 467 t-Bu H 2-Cl CF₃4-(2,6-di-Me-5-Cl-pyrimidinyl) 468 Et H 2-Me Cl 2-(3-Cl-pyridinyl)220-221 469 Me H 2-Me Cl 2-(3-Cl-pyridinyl) 217-218 470 CH₂C≡CH H2,4-di-Br Cl 2-(3-Cl-pyridinyl) 199-201 471 CH₂C≡CH H 2-Me-4-Cl Cl2-(3-Cl-pyridinyl) 219-221 472 H H 2-Me-4-Cl Cl 2-(3-Cl-pyridinyl)231-233 473 H H 2,4-di-Cl Cl 2-(3-Cl-pyridinyl) 245-247 474 CH₂C≡CH H2,4-di-Cl Cl 2-(3-Cl-pyridinyl) 166-168 475 H H 2-Me Cl2-(3-Cl-pyridinyl) 243-244 476 H H 2-Me-4-I CF₃ 2-(3-Cl-pyridinyl)241-242 477 CH₂CN H 2-Me-4-Cl Br 2-(3-Cl-pyridinyl) 225-226 478 CH₂C≡CHH 2-Me-4-Br Cl 2-(3-Cl-pyridinyl) 218-220 479 H H 2-Me-4-Br Cl2-(3-Cl-pyridinyl) 224-225 480 H H 2,4-di-Br Cl 2-(3-Cl-pyridinyl)250-252 481 i-Pr H 2-Me-4-Cl CF₃ 2-(3-Me-pyridinyl) 228-229 482 Me H2-Me-4-Cl CF₃ 2-(3-Me-pyridinyl) 226-227 483 t-Bu H 2-Me CF₃5-(1-Me-4-Cl-pyrazolyl) 216-217 484 i-Pr H 2-Me CF₃5-(1-Me-4-Cl-pyrazolyl) 220-221 485 i-Pr H 2-Me-4-(HOCH₂) CF₃2-(3-Cl-pyridinyl) 199-201 486 CH₂C≡CH H 2-Me-4-Cl CF₃2-(3-Cl-pyridinyl) 200-202 487 i-Pr, B is S H 2-Me-4-Br CF₃2-(3-Cl-pyridinyl) 214-217 488 i-Pr H 2-Me-4-CO₂Me CF₃2-(3-Cl-pyridinyl) 204-206 489 i-Pr H 2-Me-4-CONHMe CF₃2-(3-Cl-pyridinyl) 168-170 490 CH(CH₃)Ph H H CF₃ Me 212-214 491CH(CH₃)Ph H H CF₃ Et 202-203 492 CH₂CH₂N(i-Pr) H 2-Me CF₃ 2-Cl—Ph188-190 494 i-Pr H 2-Me-4-Br CF3 2-(3-Cl-pyridinyl) 197-198 495 i-Pr H2-Me 2-CH₂NHC(═O)CF₃—Ph * 496 i-Pr H 2-Me CF₃ 2-CH₂NH₂—Ph HCl * 477 i-PrH 2-Me-4-Cl CF₃ 2-(3-Cl-pyridinyl) 196-197 498 i-Pr H 2-Me CF₃2,4-di-Cl-5-OCH₂C═CH—Ph 246-249 499 t-Bu H 2-Me-4-Cl CF₃2-(3-Cl-pyridinyl) 223-225 500 Me H 2-Me-4-Cl CF₃ 2-(3-Cl-pyridinyl)148-150 (Ex. 7) 501 i-Pr H 2,4-di-Br CF₃ 2-(3-Cl-pyridinyl) 192-193 502t-Bu H 2,4-di-Br CF₃ 2-(3-Cl-pyridinyl) 246-247 505 CH₂CH₂OCH₂CH₂OH H2-Me CF₃ 2-(3-Cl-pyridinyl) 132-135 506 Me H 2,4-di-Br CF₃2-(3-Cl-pyridinyl) 162-163 507 OCH(CH₃)₂ 2-Cl CF₃ 2-Cl—Ph 218-219 508OCH(CH₃)₂ H 2-Cl CF₃ 2-(3-Cl-pyridinyl) 205-206 509 OCH(CH₃)₂ H 2-Me CF₃2-(3-Cl-pyridinyl) 210-211 510 OCH(CH₃)₂ H 2-Me CF₃ 2-Cl—Ph 196-198 511i-Pr H 2-Me CF₃ 2-CONHMe—Ph * 512 Et H 2,4-di-Br CF₃ 2-(3-Cl-pyridinyl)188-189 513 i-Pr H 2,4-di-Cl CF₃ 2-(3-Cl-pyridinyl) 200-201 514 t-Bu2,4-di-Cl CF₃ 2-(3-Cl-pyridinyl) 170-172 515 Me H 2,4-di-Cl CF₃2-(3-Cl-pyridinyl) 155-157 516 Et H 2,4-di-Cl CF₃ 2-(3-Cl-pyridinyl)201-202 517 t-Bu H 2-Me-4-Br CF₃ 2-(3-Cl-pyridinyl) 247-248 518 Et H2-Me-4-Br CF₃ 2-(3-Cl-pyridinyl) 192-193 519 i-Pr 2-Me-4-F CF₃2-(3-Cl-pyridinyl) 179-180 520 i-Pr H 2-Me-4-Br Br 2-(3-Cl-pyridinyl)185-187 521 i-Pr 2-Me-4-CF₃ CF₃ 2-(3-Cl-pyridinyl) 235-236 522 Et H2-Me-4-CF₃ CF₃ 2-(3-Cl-pyridinyl) 216-217 523 i-Pr H 2-Me-4-I CF₃2-(3-Cl-pyridinyl) 188-189 524 t-Bu H 2-Me-4-CF₃ CF₃ 2-(3-Cl-pyridinyl)148-149 525 Me H 2-Me-4-Br CF₃ 2-(3-Cl-pyridinyl) 208-210 526 i-Pr H2-Br-4-Me CF₃ 2-(3-Cl-pyridinyl) 127-128 527 t-Bu H 2-Br-4-Me CF₃2-(3-Cl-pyridinyl) 159-160 528 Et H 2-Br-4-Me CF₃ 2-(3-Cl-pyridinyl)224-225 529 Me H 2-Br-4-Me CF₃ 2-(3-Cl-pyridinyl) 208-209 530 i-Pr H2-Me-4-Cl Br 2-(3-Cl-pyridinyl) 159-161 (Ex. 10) 531 Me H 2-Me-4-Cl Br2-(3-Cl-pyridinyl) 162-164 (Ex. 11) 532 t-Bu H 2-Me-4-Cl Br2-(3-Cl-pyridinyl) 159-161 533 i-Pr H 2,4-di-Br Br 2-(3-Cl-pyridinyl)162-163 534 Me H 2,4-di-Br Br 2-(3-Cl-pyridinyl) 166-168 535 t-Bu H2,4-di-Br Br 2-(3-Cl-pyridinyl) 210-212 536 i-Pr H 2,4-di-Cl Br2-(3-Cl-pyridinyl) 188-190 537 Me H 2,4-di-Cl Br 2-(3-Cl-pyridinyl)179-180 538 Me H 2-Me-4-Br Br 2-(3-Cl-pyridinyl) 147-149 539 i-Pr H2-Cl-4-Br CF₃ 2-(3-Cl-pyridinyl) 200-202 540 t-Bu H 2-Cl-4-Br CF₃2-(3-Cl-pyridinyl) 143-145 541 Me H 2-Cl-4-Br CF₃ 2-(3-Cl-pyridinyl)171-173 542 Me H 2-Me-4-Br CF₃ 2-(3-Cl-pyridinyl) 222-223 543 i-Pr H2-Me-4-Cl Cl 2-(3-Cl-pyridinyl) 142-144 (Ex. 8) 544 Me H 2-Me-4-Cl Cl2-(3-Cl-pyridinyl) 175-177 (Ex. 9) 545 t-Bu H 2-Me-4-Cl Cl2-(3-Cl-pyridinyl) 163-165 546 i-Pr H 2-Me-4-Br Cl 2-(3-Cl-pyridinyl)152-153 547 Me H 2-Me-4-Br Cl 2-(3-Cl-pyridinyl) 140-141 548 t-Bu H2-Me-4-Br Br 2-(3-Cl-pyridinyl) 215-221 549 Me H 2-Me-4-I CF₃2-(3-Cl-pyridinyl) 199-200 550 i-Pr H 2,4-di-Br Cl 2-(3-Cl-pyridinyl)197-199 551 Me H 2,4-di-Br Cl 2-(3-Cl-pyridinyl) 188-190 552 t-Bu H2,4-di-Br Cl 2-(3-Cl-pyridinyl) 194-196 553 Et H 2,4-di-Br Cl2-(3-Cl-pyridinyl) 192-194 554 i-Pr H 2,4-di-Cl Cl 2-(3-Cl-pyridinyl)197-199 555 Me H 2,4-di-Cl Cl 2-(3-Cl-pyridinyl) 205-206 556 t-Bu H2,4-di-Cl Cl 2-(3-Cl-pyridinyl) 172-173 557 Et H 2,4-di-Cl Cl2-(3-Cl-pyridinyl) 206-208 558 Et H 2-Me-4-Cl Cl 2-(3-Cl-pyridinyl)199-200 559 Et H 2-Me-4-Cl CF₃ 2-(3-Cl-pyridinyl) 163-164 560 Et H2-Me-4-I CF₃ 2-(3-Cl-pyridinyl) 199-200 561 t-Bu H 2-Me-4-I CF₃2-(3-Cl-pyridinyl) 242-243 562 Et H 2-Me-4-Cl Br 2-(3-Cl-pyridinyl)194-195 563 Me H 2-Me-4-F CF₃ 2-(3-Cl-pyridinyl) 213-214 564 Et H2-Me-4-F CF₃ 2-(3-Cl-pyridinyl) 212-213 565 t-Bu H 2-Me-4-F CF₃2-(3-Cl-pyridinyl) 142-143 566 Me H 2-Me-4-F Br 2-(3-Cl-pyridinyl)214-215 567 Et H 2-Me-4-F Br 2-(3-Cl-pyridinyl) 204-205 568 i-Pr H2-Me-4-F Br 2-(3-Cl-pyridinyl) 206-208 569 Et H 2-Me-4-Br Cl2-(3-Cl-pyridinyl) 192-194 570 i-Pr H 2-Me-4-F Cl 2-(3-Cl-pyridinyl)184-186 571 Me H 2-Me-4-F Cl 2-(3-Cl-pyridinyl) 180-182 572 Et H2-Me-4-F Cl 2-(3-Cl-pyridinyl) 163-165 573 t-Bu H 2-Me-4-Br Cl2-(3-Cl-pyridinyl) 224-225 574 t-Bu H 2-Me-4-F Br 2-(3-Cl-pyridinyl)124-125 575 Et H 2,4-di-Br Br 2-(3-Cl-pyridinyl) 196-197 576 Me H2,4-di-Cl Br 2-(3-Cl-pyridinyl) 245-246 577 Et H 2,4-di-Cl Br2-(3-Cl-pyridinyl) 214-215 578 Et H 2-Me-4-Br Br 2-(3-Cl-pyridinyl)194-196 579 Me H 2-Me-4-I Br 2-(3-Cl-pyridinyl) 229-230 580 i-Pr H2-Me-4-I Br 2-(3-Cl-pyridinyl) 191-192 581 Me H 2-Me-4-CF₃ CF₃2-(3-Cl-pyridinyl) 249-250 582 Me H 2-Me-4-I Cl 2-(3-Cl-pyridinyl)233-235 583 Et H 2-Me-4-I Cl 2-(3-Cl-pyridinyl) 196-197 584 i-Pr H2-Me-4-I Cl 2-(3-Cl-pyridinyl) 189-190 585 t-Bu H 2-Me-4-I Cl2-(3-Cl-pyridinyl) 228-229 586 Me H 2-Me-4-Cl I 2-(3-Cl-pyridinyl)208-209 587 i-Pr H 2-Me-4-Cl I 2-(3-Cl-pyridinyl) 183-184 588 H H2-Me-4-Cl I 2-(3-Cl-pyridinyl) 228-230 589 Me H 2-Me-4-Cl Br 2-Cl-4-F—Ph250-251 590 H H 2-Me-4-Cl Br 2-Cl-4-F—Ph 229-229 591 i-Pr H 2-Me-4-Cl Br2-Cl-4-F—Ph 189-190 592 t-Bu H 2-Me-4-Cl Br 2-Cl-4-F—Ph 247-249 593 i-PrH 2-Me-4-NO₂ CF₃ 2-Cl—Ph * 594 Ph H 2-Me-4-Cl CF₃ 2-(3-Cl-pyridinyl)243-244 595 2-Me—Ph H 2-Me-4-Cl CF₃ 2-(3-Cl-pyridinyl) 249-251 596 i-PrH 2-Me-4-NO₂ CF₃ 2-(3-Cl-pyridinyl) 170-172 597 i-Pr H 2-Me-4-NO₂ CF₃2-(3-Cl-pyridinyl) * 598 Me, B is S H 2-Me CF₃ 2-Cl—Ph 164-167 599 i-PrH 2-NO₂ CF₃ 2-Cl—Ph * 600 i-Pr H 2-Me-4-Cl OCHF₂ 2-Cl—Ph 177-179 601 MeMe 2,4-di-Br Cl 2-(3-Cl-pyridinyl) 151-152 602 CH(CH₃)CH₂OCH₃ H2,4-di-Br Cl 2-(3-Cl-pyridinyl) 162-163 603 CH(CH₃)CH₂SCH₃ H 2,4-di-BrCl 2-(3-Cl-pyridinyl) 174-175 604 CH(CH₃)CH₂OH H 2,4-di-Br Cl2-(3-Cl-pyridinyl) 148-149 605 i-Pr, R1 is Me H 2-Me Br2-(3-Cl-pyridinyl) 223-225 606 i-Pr, R1 is Me H 2-Me Cl2-(3-Cl-pyridinyl) 223-225 607 i-Pr, R1 is Me H 2-Me CF₃2-(3-Cl-pyridinyl) 218-219 608 i-Pr, R1 is Me H 2-Me-4-Cl Br2-(3-Cl-pyridinyl) 231-235 609 N(CH3)₂ H 2,4-di-Br Cl 2-(3-Cl-pyridinyl)149-151 611 N(Me)₂ H 2-Me-4-Cl Br 2-(3-Cl-pyridinyl) 185-188 612 i-Pr H2-Cl CF₃ 5-(1-Me-4-Cl-pyrazolyl) 221-222 613 t-Bu H 2-Cl CF₃5-(1-Me-4-Cl-pyrazolyl) 217-218 614 CH(CH₃)CH₂CO₂Et 2,4-di-Br Cl2-(3-Cl-pyridinyl) 113-115 615 2-pyridinyl H 2-Me-4-Br CF₃2-(3-Cl-pyridinyl) 244-245 616 2-(3-Me-pyridinyl) 2-Me-4-Br CF₃2-(3-Me-pyridinyl) 182-183 619 Me, B is S H 2-Me-4-Cl Br2-(3-Cl-pyridinyl) 110-113 620 Me H 2-Me-4-Br CF₃ 2-(3-Cl-pyridinyl)207-208 621 Et H 2-Me-4-Br CF₃ 2-(3-Cl-pyridinyl) 189-190 6222-pyridinyl Et 2-Me-4-Cl CF₃ 2-(3-Cl-pyridinyl) 233-234 6232-(3-Me-pyridinyl) Me 2-Me-4-Cl CF₃ 2-(3-Cl-pyridinyl) 202-203 624 Et H2,4-di-Cl Cl 2-(3-Cl-pyridinyl) 197-198 625 Me Et 2,4-di-Cl Cl2-(3-Cl-pyridinyl) 142-143 626 CH(CH₃)CH₂SCH₃ Me 2,4-di-Cl Cl2-(3-Cl-pyridinyl) 185-186 627 Et Me 2,4-di-Br Cl 2-(3-Cl-pyridinyl)209-210 628 i-Pr Et 2-Me-4-Br CF₃ 2-(3-Cl-pyridinyl) 133-135 629 Me H2,4-di-Br Br 2-(3-Cl-pyridinyl) 185-187 630 Et H 2,4-di-Br Br2-(3-Cl-pyridinyl) 204-205 631 CH(CH₃)CH₂SCH₃ H 2,4-di-Br Br2-(3-Cl-pyridinyl) 178-179 632 Et H 2-Me-4-Cl OCHF₂ 2-(3-Cl-pyridinyl)209-211 633 i-Pr H 2-Me-4-Cl OCHF₂ 2-(3-Cl-pyridinyl) 179-181 634 Me H2-Me-4-Br OCHF₂ 2-(3-Cl-pyridinyl) 190-192 635 Et H 2-Me-4-Cl OEt2-Cl—Ph 163-165 636 i-Pr Me 2-Me-4-Cl OEt 2-Cl—Ph 173-175 637 Me Me2-Me-4-Br Ola 2-Cl—Ph 155-158 638 Et Me 2,4-di-Br Br 2-(3-Cl-pyridinyl)181-183 639 Et Me 2,4-di-Cl Cl 2-(3-Cl-pyridinyl) 162-163 640 Et Et2-Me-4-Br CF₃ 2-(3-Cl-pyridinyl) 174-175 641 Me H 2,4-di-Cl Br2-(3-Cl-pyridinyl) 216-218 642 Et Me 2,4-di-Cl Br 2-(3-Cl-pyridinyl)190-191 643 CH(CH₂)CH₂SCH₃ H 2,4-di-Cl Br 2-(3-Cl-pyridinyl) 182-183 644Et Me 2,4-di-Cl Br 2-(3-Cl-pyridinyl) 165-167 645 Et H 2-Me-4-NO₂ CF₃2-(3-Cl-pyridinyl) * 646 Me Me 2-Me-4-NO₂ CF₃ 2-(3-Cl-pyridinyl) * 647CH₂CH═CH₂ H 2-Me-4-NO₂ CF₃ 2-(3-Cl-pyridinyl) * 648 n-Pr H 2-Me-4-NO₂CF₃ 2-(3-Cl-pyridinyl) * 649 CH(CH₃)CH₂SCH₃ H 2-Me-4-NO₂ CF₃2-(3-CI-pyridinyl) * 650 Me H 2-Me-4-NO₂ CF₃ 2-(3-Cl-pyridinyl) * 651t-Bu H 2-Me-4-NO₂ CF₃ 2-(3-Cl-pyridinyl) * 652 CH₂CH₂N(Me)₂ H 2-Me-4-NO₂CF₃ 2-(3-Cl-pyridinyl) 193-195 653 CH₂CH₂N(Me)₃ ⁺I⁻ H 2-Me-4-NO₂ CF₃2-(3-Cl-pyridinyl) >250 655 N(CH₃)₂ H 2,4-di-Cl Cl 2-(3-Cl-pyridinyl)146-148 656 N(CH₃)₂ H 2,4-di-Br Br 2-(3-Cl-pyridinyl) 162-164 657N(CH₃)₂ H 2,4-di-Cl Br 2-(3-Cl-pyridinyl) 208-209 658 Et H 2-Me-4-ClOCH₂CF₃ 2-Cl—Ph 184-186 659 i-Pr H 2-Me-4-Cl OCH₂CF₃ 2-Cl—Ph 196-198 660Me H 2-Me-4-Br OCH₂CF₃ 2-Cl—Ph 220-223 661 N(CH₃)₂ H 2-Me-4-NO₂ CF₃2-(3-Cl-pyridinyl) * 662 H H 2-Me-4-Cl Br 2-(3-Cl-pyridinyl) 240-242 663n-Pr n-Pr 2-Me-4-Br CF₃ 2-(3-Cl-pyridinyl) 201-202 664 n-Pr H 2-Me-4-BrCF₃ 2-(3-Cl-pyridinyl) 188-190 665 Et Et 2-Cl CF₃ 2-(3-Cl-pyridinyl)242-243 666 n-Pr n-Pr 2,4-di-Cl Cl 2-(3-Cl-pyridinyl) 242-243 667 n-Pr H2,4-di-Cl Cl 2-(3-Cl-pyridinyl) 218-219 668 CH₂CO₂CH₂CH₃ Me 2-Me-4-BrCF₃ 2-(3-Cl-pyridinyl) 227-228 669 CH₂CO₂CH₂CH₃ Me 2,4-di-Cl Br2-(3-Cl-pyridinyl) 176-177 670 CH₂CO₂CH₂CH₃ Me 2,4-di-Br Cl2-(3-Cl-pyridinyl) 198-199 671 CH₂CO₂CH₃ H 2-Me-4-Br CF₃2-(3-Cl-pyridinyl) 141-142 672 N(CH₃)₂ H 2,4-di-Cl CF₃2-(3-Cl-pyridinyl) 136-137 673 Me Me 2,4-di-Cl CF₃ 2-(3-Cl-pyridinyl)225-227 674 Et Et 2,4-di-Cl CF₃ 2-(3-Cl-pyridinyl) 228-229 675CH₂CO₂CH₂CH₃ Me 2,4-di-Cl CF₃ 2-(3-Cl-pyridinyl) 219-220 676 Me H2-Me-4-Cl CF₃ 5-(1-Me-4-Cl-pyrazolyl) 239-241 677 i-Pr H 2-Me-4-Cl CF₃5-(1-Me-4-Cl-pyrazolyl) 252-254 678 i-Pr H 2-Me-4-Br OEt2-(3-Cl-pyridinyl) 208-211 679 Me H 2-Me-4-Br OEt 2-(3-Cl-pyridinyl)212-215 680 i-Pr H 2-Me-4-Cl OEt 2-(3-Cl-pyridinyl) 191-193 681 Et H2-Me-4-Cl OEt 2-(3-Cl-pyridinyl) 207-209 682 i-Pr H 2-Me-4-Br OCH₂CF₃2-(3-Cl-pyridinyl) 213-215 683 Me H 2-Me-4-Br OCH₂CF₃ 2-(3-Cl-pyridinyl)206-208 684 i-Pr H 2-Me-4-Cl OCH₂CF₃ 2-(3-Cl-pyridinyl) 211-213 685 Et H2-Me-4-Cl OCH₂CF₃ 2-(3-Cl-pyridinyl) 205-207 686 Me H 2-Me-4-Cl OCH₂CF₃2-(3-Cl-pyridinyl) 195-197 (Ex. 12) 687 Et H 2-Me-4-Br OCH₂CF₃2-(3-Cl-pyridinyl) 208-211 688 t-Bu H 2-Me-4-Br OCH₂CF₃2-(3-Cl-pyridinyl) 213-216 689 i-Pr H 2-Me-4-Br CF₃5-(1-Me-4-Cl-pyrazolyl) 256-258 690 t-Bu H 2-Me-4-Br CF₃5-(1-Me-4-Cl-pyrazolyl) 254-256 691 Me Me 2,4-di-Br CF₃2-(3-Cl-pyridinyl) 228-229 692 i-Pr H 2-Me-4-Cl OCF₂CHF₂2-(3-Cl-pyridinyl) 189-192 693 Et H 2-Me-4-Cl OCF₂CHF₂2-(3-Cl-pyridinyl) 189-192 694 Me H 2-Me-4-Cl OCF₂CHF₂2-(3-Cl-pyridinyl) 162-165 695 i-Pr H 2-Me-4-Br OCF₂CHF₂2-(3-Cl-pyridinyl) 185-188 696 Et H 2-Me-4-Br OCF₂CHF₂2-(3-Cl-pyridinyl) 195-198 697 Me H 2-Me-4-Br OCF₂CHF₂2-(3-Cl-pyridinyl) 164-167 698 Me Me 2-Cl-4-Br CF₃ 2-(3-Cl-pyridinyl)238-239 699 Et Me 2-Cl-4-Br CF₃ 2-(3-Cl-pyridinyl) 216-217 700 H H H CF₃2-(3-Cl-pyridinyl) 701 Et H 2-Me-4-Br CF₃ 5-(1-Me-4-Cl-pyrazolyl)249-251 702 i-Pr H 2,4-di-Cl OCH₂CF₃ 2-(3-Cl-pyridinyl) 232-235 703 Me H2,4-di-Cl OCH₂CF₃ 2-(3-Cl-pyridinyl) 192-195 704 Me Me 2,4-di-Cl OCH₂CF₃2-(3-Cl-pyridinyl) 132-135 705 i-Pr H 2,4-di-Br OCH₂CF₃2-(3-Cl-pyridinyl) 225-227 706 Me H 2.4-di-Br OCH₂CF₃ 2-(3-Cl-pyridinyl)206-208 707 Me Me 2,4-di-Br OCH₂CF₃ 2-(3-Cl-pyridinyl) 175-177 708 Me H2-Cl-4-Br Br 2-(3-Cl-pyridinyl) 226-227 709 Me Me 2-Cl-4-Br Br2-(3-Cl-pyridinyl) 237-238 710 Me H 2-Cl-4-Br Cl 2-(3-Cl-pyridinyl)228-229 711 Me Me 2-Cl-4-Br Cl 2-(3-Cl-pyridinyl) 236-237 712CH₂C(Me)₂CH₂N—(Me)₂ H 2-Me CF₃ 2-(3-Cl-pyridinyl) 197-200 713 Me H2-Me-4-Br CF₃ 5-(1-Me-4-Cl-pyrazolyl) 242-244 714 Et H 2-Me-4-Cl CF₃5-(1-Me-4-Cl-pyrazolyl) 252-254 715 t-Bu H 2-Me-4-Cl CF₃5-(1-Me-4-Cl-pyrazolyl) 259-260 716 i-Pr H 2,4-di-Cl OCBrF₂2-(3-Cl-pyridinyl) 220-222 717 Me H 2,4-di-Cl OCBrF₂ 2-(3-Cl-pyridinyl)188-191 718 Me Me 2,4-di-Cl OCBrF₂ 2-(3-Cl-pyridinyl) 203-205 719 Me H2-Me-4-Cl OCHF₂ 2-(3-Cl-pyridinyl) 210-212 720 i-Pr H 2-Me-4-Cl OCBrF₂2-(3-Cl-pyridinyl) 194-196 721 Me H 2-Me-4-Cl OCBrF₂ 2-(3-Cl-pyridinyl)181-183 722 Me H 3,4-di-F Cl 2-(3-Cl-pyridinyl) 202-203 723 Me Me3,4-di-F Cl 2-(3-Cl-pyridinyl) 251-252 724 Me Me 2-Me-4-F Cl2-(3-Cl-pyridinyl) 242-243 725 Me Me 2-Cl-4-F Br 2-(3-Cl-pyridinyl)245-246 726 Me H 2-Cl-4-F Br 2-(3-Cl-pyridinyl) 217-218 727 i-Pr H2-Cl-4-F Br 2-(3-Cl-pyridinyl) 168-169 728 Me Me 2-Cl-4-F Cl2-(3-Cl-pyridinyl) 239-240 729 Me H 2-Cl-4-F Cl 2-(3-Cl-pyridinyl)248-249 730 i-Pr H 2-Cl-4-F Cl 2-(3-Cl-pyridinyl) 169-170 731 Me Me2-Cl-4-F CF₃ 2-(3-Cl-pyridinyl) 215-216 732 Me H 2-Cl-4-F CF₃2-(3-Cl-pyridinyl) 219-220 733 Me Me 2-Br-4-F Br 2-(3-Cl-pyridinyl)235-236 734 Me H 2-Br-4-F Br 2-(3-Cl-pyridinyl) 238-239 735 i-Pr H2-Br-4-F Br 2-(3-Cl-pyridinyl) 236-237 736 Me Me 2-Br-4-F Cl2-(3-Cl-pyridinyl) 246-247 737 Me H 2-Br-4-F Cl 2-(3-Cl-pyridinyl)233-234 738 i-Pr H 2-Br-4-F Cl 2-(3-Cl-pyridinyl) 153-154 739 i-Pr H2-Me-4-Cl OCHMe₂ 2-(3-Cl-pyridinyl) 208-210 740 Me H 2-Me-4-Cl OCHMe₂2-(3-Cl-pyridinyl) 207-210 741 i-Pr H 2,4-di-Cl OCHMe₂2-(3-Cl-pyridinyl) 187-191 742 Me H 2,4-di-Cl OCHMe₂2-(3-Cl-pyridinyl) * 743 Me Me 2-Br-4-F CF₃ 2-(3-Cl-pyridinyl) 191-192744 Me H 2-Br-4-F CF₃ 2-(3-Cl-pyridinyl) 228-229 745 i-Pr H 2-Br-4-F CF₃2-(3-Cl-pyridinyl) 224-226 746 Me Me 2-Br-4-Cl Br 2-(3-Cl-pyridinyl)188-189 747 Me H 2-Br-4-Cl Br 2-(3-Cl-pyridinyl) 248-249 748 i-Pr H2-Br-4-Cl Br 2-(3-Cl-pyridinyl) 252-253 749 Me Me 2-Br-4-Cl Cl2-(3-Cl-pyridinyl) 147-148 750 Me H 2-Br-4-Cl Cl 2-(3-Cl-pyridinyl)249-250 751 i-Pr H 2-Br-4-Cl Cl 2-(3-Cl-pyridinyl) 239-240 752 Me Me2-Br-4-Cl CF₃ 2-(3-Cl-pyridinyl) 200-201 753 Me H 2-Br-4-Cl CF₃2-(3-Cl-pyridinyl) 158-159 754 i-Pr H 2-Br-4-Cl CF₃ 2-(3-Cl-pyridinyl)250-250 755 Me Me 2-Me-4-Cl Cl 2-(3-Cl-pyridinyl) 232-233 756 Me H 2-CF₃CF₃ 2-(3-Cl-pyridinyl) 218-220 757 i-Pr H 2-CF₃ CF₃ 2-(3-Cl-pyridinyl)242-246 758 Me Me 2-CF₃ CF₃ 2-(3-Cl-pyridinyl) 239-244 759 Me Me2-Me-4-Cl Br 2-(3-Cl-pyridinyl) 210-211 760 Me Me 2.4-di-Me Cl2-(3-Cl-pyridinyl) 223-224 761 Me Me 2,4-di-Me Br 2-(3-Cl-pyridinyl)240-241 762 Me H 2-F Br 2-(3-Cl-pyridinyl) 215-216 763 i-Pr H 2-F Br2-(3-Cl-pyridinyl) 213-215 764 i-Pr H 2-CF3-4-Cl CF₃ 2-(3-Cl-pyridinyl)254-256 765 Me Me 2-CF3-4-Cl CF₃ 2-(3-Cl-pyridinyl) 229-231 766 Me H2-CF3-4-Cl CF₃ 2-(3-Cl-pyridinyl) 235-237 767 Me H 2,4-di-Cl CF₃2-(3-Cl-pyridinyl), R⁸ is Cl 225-226 768 i-Pr H 2,4-di-Cl CF₃2-(3-Cl-pyridinyl), R⁸ is Cl 230-232 769 Me Me 2,4-di-Cl CF₃2-(3-Cl-pyridinyl), R⁸ is Cl 194-196 770 i-Pr H 2-Me-4-Cl CF₃3-isoxazolyl 255-257 771 Me H 2,4-di-F Br 2-(3-Cl-pyridinyl) 197-198 772Me Me 2,4-di-F Br 2-(3-Cl-pyridinyl) 218-222 773 Me H 2-F Cl2-(3-Cl-pyridinyl) 185-187 774 Me H 2-F-4-Cl Br 2-(3-Cl-pyridinyl)203-204 775 Me Me 2-F-4-Cl Br 2-(3-Cl-pyridinyl) 226-227 776 i-Pr H2-F-4-Cl Br 2-(3-Cl-pyridinyl) 207-208 777 Me H 2-F-4-Cl Cl2-(3-Cl-pyridinyl) 211-212 778 Me Me 2-F-4-Cl Cl 2-(3-Cl-pyridinyl)237-238 779 i-Pr H 2-Me-4-CN CF₃ 2-(3-Cl-pyridinyl) * 780 H H 2-F-4-ClCl 2-(3-Cl-pyridinyl) 116-117 781 Me H 2,4-di-F Cl 2-(3-Cl-pyridinyl)159-160 782 Me Me 2,4-di-F Cl 2-(3-Cl-pyridinyl) 225-226 783 i-Pr H2,4-di-F Cl 2-(3-Cl-pyridinyl) 201-202 784 H H 2,4-di-F Cl2-(3-Cl-pyridinyl) 128-129 785 Et H 2-Me-4-Cl CF₃ 5-(1-CH₂CF₃-pyrazolyl)172-174 786 Me H 2-Me-4-Cl CF₃ 5-(1-CH₂CF₃-pyrazolyl) 192-194 787 Me H2,4-di-Cl F 2-(3-Cl-pyridinyl) * 788 Me H 2-F OCH₂CF₃ 2-(3-Cl-pyridinyl)202-203 789 Me Me 2-F OCH₂CF₃ 2-(3-Cl-pyridinyl) 178-179 790 i-Pr H 2-FOCH₂CF₃ 2-(3-Cl-pyridinyl) 161-162 791 Me H 2-F-4-Br Br2-(3-Cl-pyridinyl) 209-210 792 Me Me 2-F-4-Br Br 2-(3-Cl-pyridinyl)225-226 793 i-Pr H 2-F-4-Br Br 2-(3-Cl-pyridinyl) 208-209 794 Me H2-F-4-Br Cl 2-(3-Cl-pyridinyl) 209-210 795 Me Me 2-F-4-Br Cl2-(3-Cl-pyridinyl) 244-245 796 Me Me 2-F-4-Br Cl 2-(3-Cl-pyridinyl)207-208 797 Me H 2-F-4-Br OCH₂CF₃ 2-(3-Cl-pyridinyl) 210-211 798 Me Me2-F-4-Br OCH₂CF₃ 2-(3-Cl-pyridinyl) 204-206 799 i-Pr H 2,4-di-Cl CF₃3-(4-Cl-5-Me-isoxazolyl) 204-205 800 Me H 2,4-di-Cl CF₃3-(4-Cl-5-Me-isoxazolyl) 131-132 801 i-Pr H 2-Me-4-Cl CF₃3-(4-Cl-5-Me-isoxazolyl) 188-189 802 Me H 2-Me-4-Cl CF₃3-(4-Cl-5-Me-isoxazolyl) 210-211 803 i-Pr H 2,4-di-Cl CF₃3-(4-Cl-isoxazolyl) 212-213 804 i-Pr H 2-Me-4-Cl CF₃ 3-(4-Cl-isoxazolyl)232 805 Me H 2-Me-4-Cl CF₃ 3-(4-Cl-isoxazolyl) 190-191 806 Me H2,4-di-Cl CF₃ 3-(4-Cl-isoxazolyl) 209-210 807 i-Pr H 4-Cl CF₃3-(4-Cl-isoxazolyl) 241-242 808 i-Pr H 2,4-di-Cl CF₃5-(1-CH₂CF₃-pyrazolyl) 212-214 809 H H 2,4-di-Cl F 2-(3-Cl-pyridinyl) *810 i-Pr H 2,4-di-Cl F 2-(3-Cl-pyridinyl) * 811 Me Me 2,4-di-Cl F2-(3-Cl-pyridinyl) * 812 H H 2-Me-4-Cl F 2-(3-Cl-pyridinyl) * 813 i-Pr H2-Me-4-Cl F 2-(3-Cl-pyridinyl) * 814 Me H 2-Me-4-Cl F2-(3-Cl-pyridinyl) * 815 Me Me 2-Me-4-Cl F 2-(3-Cl-pyridinyl) * 816 Me H2,4-di-Cl CF₃ 5-(1-Me-4-Cl-pyrazolyl) 242-244 817 Et H 2,4-di-Cl CF₃5-(1-Me-4-Cl-pyrazolyl) 266-268 818 i-Pr H 2,4-di-Cl CF₃5-(1-Me-4-Cl-pyrazolyl) 241-243 819 Me Me 2,4-di-Cl CF₃5-(1-Me-4-Cl-pyrazolyl) 202-204 820 t-Bu H 2,4-di-Cl CF₃5-(1-Me-4-Cl-pyrazolyl) 128-131 821 Me H 2,4-di-Cl CF₃2-(3-Cl-pyridinyl) * 822 H H 2-F-4-Br Br 2-(3-Cl-pyridinyl) 151-152 823H H 2-Cl-4-F Cl 2-(3-Cl-pyridinyl) 133-134 824 Me H 2,4-di-F F2-(3-Cl-pyridinyl) 166-167 825 H H 2-F-4-Br Cl 2-(3-Cl-pyridinyl)148-149 826 H H 2-Br-4-Cl Br 2-(3-Cl-pyridinyl) 134-136 827 Me Me2,4-di-F F 2-(3-Cl-pyridinyl) 211-212 828 H H 2,4-di-F F2-(3-Cl-pyridinyl) 115-117 829 i-Pr H 2,4-di-F F 2-(3-Cl-pyridinyl)157-158 830 i-Pr H 2-Cl-4-I Cl 2-(3-Cl-pyridinyl) 192-195 831 i-Pr H2,4-di-Cl OCH₃ 2-(3-Cl-pyridinyl) 191-194 832 Me H 2,4-di-Cl OCH₃2-(3-Cl-pyridinyl) 143-145 833 Me H 2-Me-4-Cl Br 2-(3-Cl-5-Br-pyridinyl)216-219 834 Me H 2-F F 2-(3-Cl-pyridinyl) 217-218 835 Me H 2-Cl-4-F F2-(3-Cl-pyridinyl) 207-208 836 Me Me 2-Cl-4-F F 2-(3-Cl-pyridinyl)221-222 837 i-Pr H 2-C-4-F F 2-(3-Cl-pyridinyl) 166-167 838 H H 2-Cl-4-FF 2-(3-Cl-pyridinyl) 133-134 839 Me H 2-F-4-I Br 2-(3-Cl-pyridinyl)216-217 840 Me Me 2-F-4-I Br 2-(3-Cl-pyridinyl) 218-219 841 i-Pr H2-F-4-I Br 2-(3-Cl-pyridinyl) 217-218 842 H H 2,4-di-F Br2-(3-Cl-pyridinyl) 178-179 843 Me H 2-I-4-F F 2-(3-Cl-pyridinyl) 217-218844 Me Me 2-I-4-F F 2-(3-Cl-pyridinyl) 238-239 845 H H 2-Me-4-Cl CF₃2-(3-F-pyridinyl) * 846 Me H 2-Me-4-Cl CF₃ 2-(3-F-pyridinyl) * 847 Me Me2-Me-4-Cl CF₃ 2-(3-F-pyridinyl) * 848 i-Pr H 2-Me-4-Cl CF₃2-(3-F-pyridinyl) * 849 H H 2,4-di-Cl CF₃ 2-(3-F-pyridinyl) * 850 Me Me2,4-di-Cl CF₃ 2-(3-F-pyridinyl) * 851 i-Pr H 2,4-di-Cl CF₃2-(3-F-pyridinyl) * 852 H H 2,4-di-Cl Br 2-(3-F-pyridinyl) * 853 Me H2,4-di-Cl Br 2-(3-F-pyridinyl) * 854 Me Me 2,4-di-Cl Br2-(3-F-pyridinyl) * 855 i-Pr H 2,4-di-Cl Br 2-(3-F-pyridinyl) * 856 H H2-Me-4-Cl Br 2-(3-F-pyridinyl) * 857 Me H 2-Me-4-Cl Br2-(3-F-pyridinyl) * 858 Me Me 2-Me-4-Cl Br 2-(3-F-pyridinyl) * 859 i-PrH 2-Me-4-Cl Br 2-(3-F-pyridinyl) * 860 Me H 2,4-di-Cl CF₃5-(1-CH₂CF₃-4-Cl-pyrazolyl) 181-183 *See Index Table B ¹H NMR data R¹,R⁵, and R⁸ are H, except where indicated; B is O, except whereindicated. “CN” is bonded through carbon, not nitrogen; for example“CN—Ph” specifies cyanophenyl, not isocyanophenyl

INDEX TABLE B Compound ¹H NMR Data (CDCl₃ solution unless indicatedotherwise)^(a) 191 (DMSO-d₆) δ 1.03 (d, 6H), 2.18 (s, 3H), 3.92 (m, 1H),7.22-7.30 (m, 2H), 7.35 (m, 1H), 7.62 (dd, 1H), 7.81 (s, 1H), 8.02 (d,1H), 8.15 (dd, 1H), 8.55 (dd, 1H), 10.34 (s, 1H). 224 (DMSO-d₆) δ 1.01(d, 6H), 2.16 (s, 3H), 3.92 (m, 1H), 7.27 (m, 2H), 7.35 (m, 1H), 7.89(s, 1H), 7.96 (m, 1H), 8.37 (s, 2H), 10.42 (s, 1H). 248 (DMSO-d₆) δ 1.04(d, 6H), 4.0 (m, 1H), 7.4 (m, 2H), 7.5 (m, 1H), 7.6 (m, 1H), 7.78 (d,2H), 8.0 (d, 2H), 8.2(d, 1H), 10.7 (bs, 1H). 249 (DMSO-d₆) δ 1.16 (d,6H), 4.1 (m, 1H), 5.9 (d, 1H), 7.1 (m, 1H), 7.2 (m, 3H), 7.69 (s, 1H),7.73 (s, 1H), 10.45 (s, 1H). 250 (DMSO-d₆) δ 1.0 (d, 6H), 3.9 (m, 1H),7.4 (m, 2H), 7.6 (m, 1H), 7.8 (m, 2H), 8.0 (d, 1H), 8.1 (d, 1H), 8.3 (s,1H), 10.6 (s, 1H). 251 (DMSO-d₆) δ 1.0 (d, 6H), 4.0 (m, 1H), 7.1 (m,1H), 7.43 (m, 2H), 7.5 (m, 4H), 7.66 (m, 2H), 10.6 (s, 1H). 254(DMSO-d₆) δ 1.02 (d, 6H), 2.18 (s, 3H), 3.9-4.0 (m, 1H), 7.2 (m, 1H),7.4 (m, 1H), 7.8-7.9 (m, 2H), 8.0 (d, 2H), 8.3 (s, 1H), 10.3 (s, 1H).255 (DMSO-d₆) δ 1.02 (d, 6H), 2.18 (s, 3H), 3.9-4.0 (m, 1H), 7.2 (m,1H), 7.4 (m, 1H), 7.8-7.9 (m, 2H), 8.0 (d, 2H), 8.3 (s, 1H), 10.3 (s,1H). 256 (DMSO-d₆) δ 1.04 (d, 6H), 4.0 (m, 1H), 7.4 (m, 2H), 7.76 (s,1H), 7.7 (m, 1H), 7.74 (m, 1H), 7.9 (m, 1H), 7.97 (d, 1H), 8.07 (s, 1H),8.2 (m, 1H, 10.7 (bs, 1H). 271 (DMSO-d₆) δ 1.0 (d, 6H), 2.01 (s, 3H),2.17 (s, 3H), 3.9 (m, 1H), 7.3 (m, 2H), 7.3-7.4 (m, 1H), 7.8-7.9 (s,1H), 7.9-8.0 (m, 2H), 8.1-8.2 (s, 1H), 10.3-10.4 (s, 1H). 280 (DMSO-d₆)δ 1.21 (d, 6H), 2.24 (s, 3H), 4.1-4.3 (m, 1H), 5.9 (d, 1H), 7.02 (d,1H), 7.1-7.6 (m, 7H), 7.78 (s, 1H), 10.0 (br s, 1H). 281 (DMSO-d₆) δ1.03 (d, 6H), 1.94 (s, 3H), 2.14 (s, 3H), 3.9-4.0 (m, 1H), 7.1- 7.4 (m,8H), 7.8 (s, 1H), 7.9-8.0 (d, 1H), 10.0 (s, 1H). 282 (DMSO-d₆) δ 1.04(d, 6H), 2.18 (s, 3H), 3.9-4.0 (m, 1H), 7.2-7.4 (m, 6H), 7.4-7.6 (m,2H), 7.9 (s, 1H), 7.9-8.0 (d, 1H), 10.1 (br s, 1H). 285 δ 1.20 (d, 6H),2.19 (s, 3H), 4.2 (m, 1H), 5.9-6.0 (d, 1H), 7.1-7.5 (m, 8H), 10.4-10.5(s, 1H). 321 (DMSO-d₆) δ 1.03 (d, 6H), 2.18 (s, 3H), 3.31 (s, 3H),3.9-4.0 (m, 1H), 7.2-7.3 (m, 2H), 7.3-7.4 (m, 1H), 7.81 (s, 1H), 7.9 (d,1H), 8.0 (brd, 1H), 8.1 (dd, 1H), 8.3 (d, 1H), 10.3 (s, 1H). 405 δ 2.57(t, 2H), 3.57 (q, 2H), 6.25 (t, 1H), 7.18-7.53 (m, 8H), 9.17 (s, 1H) 406δ 1.23 (d, 6H), 4.13 (m, 1H), 5.92 (d, 1H), 7.35 (m, 1H), 7.39 (s, 1H)7.42 (m, 2H), 7.92 (d, 1H), 8.51 (d, 1H), 10.23 (br s, 1H). 409 δ 1.13(d, 6H), 4.15 (m, 1H), 5.99 (d, 1H), 7.40 (m, 1H), 7.41 (m, 1H), 76.3(m, 1H), 7.80 (s, 1H), 7.90 (d, 1H), 8.48 (d, 1H), 10.2 (br s, 1H). 495δ 1.22 (d, 6H), 2.18 (s, 3H), 4.15 (m, 1H), 4.37 (s, 1H), 5.91 (d, 1H),7.20 (m, 4H), 7.30 (m, 1H), 7.40 (m, 1H), 7.52 (m, 2H), 7.96 (s, 1H),10.23 (s, 1H). 496 (DMSO-d₆) δ 1.05 (d, 6H), 2.15 (s, 3H), 3.74 (s, 2H),3.93 (m, 1H), 7.26- 7.70 (m, 8H), 8.05 (s, 1H), 8.35 (br s, 2H), 10.45(s, 1H). 511 δ 1.20 (d, 6H), 2.01 (s, 3H), 2.72 (d, 3H), 4.13 (m, 1H),6.01 (d, 1H), 6.45 (s, 1H), 7.17 (m, 5H), 7.51 (m, 2H), 7.63 (m, 1H),10.41 (s, 1H). 593 (DMSO-d₆) δ 1.04 (d, 6H), 2.32 (s, 3H), 3.91 (m, 1H),7.44-7.64 (m, 4H), 7.77 (s, 1H), 8.07 (d, 1H), 8.27 (d, 1H), 8.42 (d,1H), 10.6 (s, 1H). 597 (DMSO-d₆) δ 1.03 (d, 6H), 3.88 (m, 1H), 7.65 (dd,1H), 7.88 (s, 1H), 8.18 (s, 1H), 8.22 (d, 1H), 8.48-8.57 (m, 3H), 10.95(s, 1H). 599 δ 1.24 (d, 6H), 4.22 (m, 1H), 5.98 (br d, 1H), 7.30-7.55(m, 6H), 7.78 (d, 1H), 7.99 (d, 1H), 11.15 (s, 1H). 645 δ 1.30 (t, 3H),2.32 (s, 3H), 3.55 (q, 2H), 6.23 (br t, 1H), 7.30 (s, 1H), 7.42 (dd,1H), 7.91 (d, 1H), 8.20 (apparent s, 2H), 8.52 (d, 1H), 10.92 (s, 1H).646 δ 2.21 (s, 3H), 2.90 (s, 3H), 3.12 (s, 3H), 7.42 (m, 2H), 7.92 (d,1H), 7.92 (d, 1H), 8.00 (d, 1H), 8.50 (d, 1H), 9.92 (br s, 1H). 647 δ2.32 (s, 3H), 4.02 (t, 2H), 5.18-5.30 (m, 2H), 5.82-5.98 (m, 1H), 7.37(s, 1H), 7.43 (dd, 1H), 7.50 (brt, 1H), 7.92 (d, 1H), 8.17 (s, 1H), 8.37(d, 1H), 8.52 (d, 1H), 11.12 (br s, 1H). 648 δ 0.91 (t, 3H), 1.63 (m,2H), 2.31 (s, 3H), 3.40 (q, 2H), 6.83 (br t, 1H), 7.35 (s, 1H), 7.42(dd, 1H), 7.91 (d, 1H), 8.17 (d, 1H), 8.24 (d, 1H), 8.52 (d, 1H), 11.03(s, 1H). 649 δ 1.38 (d, 3H), 2.14 (s, 3H), 2.35 (s, 3H), 2.72 (m, 2H),4.38 (m, 1H), 6.93 (br d, 1H), 7.33 (s, 1H), 7.43 (dd, 1H), 7.91 (d,1H), 8.18 (d, 1H), 8.28 (d, 1H), 8.52 (d, 1H), 10.93 (s, 1H). 650(DMSO-d₆) δ 2.32 (s, 3H, 2.70 (s, 3H), 7.63 (m, 2H), 7.78 (br s, 1H),8.18 (br s, 1H), 8.21 (d, 1H), 8.27 (br s, 1H), 8.58 (m, 2H). 651(DMSO-d₆) δ 1.25 (s, 9H), 2.31 (s, 3H), 7.64 (dd, 1H), 7.79 (s, 1H),8.03 (br s, 2H), 8.22 (d, 1H), 8.28 (s, 1H), 8.54 (d, 1H), 10.62 (s,1H). 661 δ 2.33 (s, 3H), 2.75 (br s, 6H), 6.9 (br s, 1H), 7.33 (dd, 1H),7.91 (d, 1H), 8.19 (br s, 1H), 8.23 (s, 1H), 8.50 (d, 1H), 10.70 (br s1H). 742 δ 1.39 (d, 6H), 2.81 (d, 3H), 4.95 (m, 1H), 6.59 (s, 1H), 6.62(q, 1H), 7.12 (s, 1H), 7.24 (s, 1H), 7.29 (t, 1H), 7.80 (d, 1H), 8.40(d, 1H), 9.56 (br s, 1H). 779 δ 1.24 (d, 6H), 2.22 (s, 3H), 4.20 (m,1H), 6.10 (d, 1H), 7.35 (s, 1H), 7.44 (t, 1H), 7.55 (s, 2H), 7.87 (s,1H), 8.48 (d, 1H), 10.7 (s, 1H). 787 δ 2.91 (d, 3H), 6.3 (m, 1H), 6.77(d, 1H), 7.3 (obscured, 1H), 7.3-7.4 (m, 2H), 7.8-7.9 (d, 1H), 8.5 (dm1H), 9.6-9.7 (br s, 1H). 809 (DMSO-d₆) δ 7.1 (d, 1H), 7.5-7.7 (m, 3H),7.8 (m, 2H), 8.1-8.2 (d, 1H), 8.5 (d, 1H), 10.5 (br s, 1H). 810(DMSO-d₆) δ 1.03 (d, 6H), 3.9 (m, 1H), 7.1 (d, 1H), 7.4-7.5 (d, 1H), 7.6(dd, 1H), 7.8 (d, 1H), 8.2 (d, 1H), 8.2 (m, 1H), 8.5 (d, 1H), 10.5 (brs, 1H). 811 δ 2.78 (s, 3H), 3.04 (s, 3H), 6.9 (d, 1H), 7.1 (d, 1H), 7.29(d, 1H), 7.3-7.4 (dd, 1H), 7.8-7.9 (d, 1H), 8.5 (d, 1H), 9.8 (br s, 1H).812 δ 2.18 (s, 3H), 5.7 (br s, 1H), 6.2 (br s, 1H), 6.7 (d, 1H), 7.3 (m,1H), 7.3- 7.4 (dd, 1H), 7.8-7.9 (d, 1H), 8.4-8.5 (d, 1H), 10.0 (br s,1H). 813 δ 1.23 (d, 6H), 2.19 (s, 3H), 4.2 (m, 1H), 5.9 (br s, 1H), 6.7(d, 1H), 7.21 (d, 1H), 7.26 (obscured, 1H), 7.3-7.4 (dd, 1H), 7.8-7.9(d, 1H), 8.4-8.5 (d, 1H), 10.1 (br s, 1H). 814 δ 2.20 (s, 3H), 2.96 (d,3H), 6.1 (br s, 1H), 6.65 (d, 1H), 7.2 (d, 1H), 7.26 (obscured, 1H),7.3-7.4 (dd, 1H), 7.8-7.9 (d, 1H), 8.4-8.5 (d, 1H), 10.1 (br s, 1H). 815δ 2.06 (s, 3H), 2.78 (s, 3H), 3.08 (s, 3H), 6.9 (d, 1H), 7.0 (s, 1H),7.1 (s, 1H), 7.3-7.4 (dd, 1H), 7.8-7.8 (d, 1H), 8.4-8.5 (d, 1H), 9.7-9.8(br s, 1H). 821 (DMSO-d₆) δ 2.65 (d, 3H), 7.52 (d, 1H), 7.6-7.8 (m, 2H),7.9 (d, 1H), 8.0-8.1 (t, 1H), 8.3-8.4 (m, 1H), 8.4 (d, 1H), 10.7 (br s,1H). 845 (DMSO-d₆) δ 2.18 (s, 3H), 7.41 (d, 1H), 7.5 (m, 2H), 7.67 (s,1H), 7.7 (m, 1H), 7.8 (s, 1H), 8.0-8.1 (t, 1H), 8.4 (d, 1H), 10.4-10.5(br s, 1H). 846 (DMSO-d₆) δ 2.18 (s, 3H), 2.66 (d, 3H), 7.35 (d, 1H),7.49 (d, 1H), 7.69, (s, 1H), 7.7-7.8 (m, 1H), 8.0-8.1 (t, 1H), 8.3 (m,1H), 8.4 (d, 1H), 10.4- 10.5 (br s, 1H). 847 δ 2.00 (s, 3H), 2.75 (s,3H), 3.09 (s, 3H), 6.99 (d, 1H), 7.03 (s, 1H), 7.4-7.5 (m, 1H), 7.5-7.6(t, 1H), 7.76 (d, 1H), 8.4 (d, 1H), 10.4-10.5 (br s, 1H). 848 (DMSO-d₆)δ 1.02 (d, 6H), 2.19 (s, 3H), 3.9 (m, 1H), 7.30 (s, 1H), 7.48 (d, 1H),7.6-7.8 (m, 2H), 8.0 (t, 1H), 8.1 (d, 1H), 8.4 (d, 1H), 10.4 (br s, 1H).849 (DMSO-d₆) δ 7.59 (d, 1H), 7.6 (s, 1H), 7.7-7.8 (m, 2H), 7.9 (m, 2H),8.0- 8.1 (t, 1H), 8.4 (d, 1H), 10.6-10.7 (br s, 1H). 850 δ 2.79 (s, 3H),3.08 (s, 3H), 7.09 (d, 1H), 7.25 (d, 1H), 7.4-7.5 (m, 1H), 7.5- 7.6 (t,1H), 7.78 (s, 1H), 8.4 (d, 1H), 10.5 (br s, 1H). 851 (DMSO-d₆) δ 1.01(d, 6H), 3.9 (m, 1H), 7.46 (d, 1H), 7.7 (m, 1H), 7.8 (s, 1H), 7.85 (d,1H), 8.0 (t, 1H), 8.2-8.3 (d, 1H), 8.4 (d, 1H), 10.6-10.7 (br s, 1H).852 (DMSO-d₆) δ 7.39 (s, 1H), 7.55 (d, 1H), 7.4 (s, 1H), 7.4-7.5 (m,1H), 7.8 (s, 1H), 7.85 (d, 1H), 8.0 (t, 1H), 8.4 (d, 1H), 10.5 (br s,1H). 853 (DMSO-d₆) δ 2.66 (d, 3H), 7.40 (s, 1H), 7.51 (d, 1H), 7.6-7.7(m, 1H), 7.84 (d, 1H), 8.0 (t, 1H), 8.3-8.4 (m, 1H), 8.4 (d, 1H),10.5-10.6 (br s, 1H). 854 δ 2.80 (s, 3H), 3.07 (s, 3H), 7.10 (s, 1H),7.31 (d, 1H), 7.35 (s, 1H), 7.4 (m, 1H), 7.5-7.6 (t, 1H), 8.4 (d, 1H),9.5 (br s, 1H). 855 (DMSO-d₆) δ 1.02 (d, 6H), 3.9 (m, 1H), 7.45(apparent s, 2H), 7.6-7.7 (m, 1H), 7.84 (d, 1H), 7.9-8.0 (t, 1H), 8.2(d, 1H), 8.36 (d, 1H), 10.5 (br s, 1H). 856 (DMSO-d₆) δ 2.17 (s, 3H),7.33 (s, 1H), 7.4 (d, 1H), 7.5 (m, 2H), 7.6-7.7 (m, 1H), 7.9 (s, 1H),8.0 (t, 1H), 8.4 (d, 1H), 10.3 (br s, 1H). 857 (DMSO-d₆) δ 2.17 (s, 3H),2.67 (d, 3H), 7.3-7.4 (m, 2H), 7.5 (d, 1H), 7.6- 7.7 (m, 1H), 8.0 (t,1H), 8.2-8.3 (m, 1H), 8.4 (d, 1H), 10.3 (br s, 1H). 858 δ 2.08 (s, 3H),2.79 (s, 3H), 3.09 (s, 3H), 6.99 (d, 1H), 7.11 (s, 1H), 7.28 (d, 1H), 74(m, 1H), 7.5-7.6 (t, 1H), 8.3-8.4 (d, 1H), 9.8 (br s, 1H). 859 (DMSO-d₆)δ 1.03 (d, 6H), 2.17 (s, 3H), 3.9 (m, 1H), 7.3 (d, 1H), 7.37 (s, 1H),7.5 (d, 1H), 7.6-7.7 (m, 1H), 7.9-8.0 (t, 1H), 8.1 (d, 1H), 8.3-8.4 (d,1H), 10.2-10.3 (br s, 1H). ^(a1)H NMR data are in ppm downfield fromtetramethylsilane. Couplings are designated by (s)-singlet, (d)-doublet,(t)-triplet, (q)-quartet, (m)-multiplet, (dd)-doublet of doublets,(dt)-doublet of triplets, (br s)-broad singlet.

Biological Examples of the Invention Test A

For evaluating control of fall armyworm (Spodoptera frugiperda) the testunit consisted of a small open container warn a 4-5-day-old corn (maize)plant inside. This was pre-infested with 10-15 1-day-old larvae in apiece of insect diet by use of a core sampler to remove a plug from asheet of hardened insect diet having many larvae growing on it andtransfer the plug containing larvae and diet to the test unit. Thelarvae moved onto the test plant as the diet plug dried out.

Test compounds were formulated using a solution containing 10% acetone,90% water and 300 ppm X-77® Spreader Lo-Foam Formula non-ionicsurfactant containing alkylarylpolyoxyethylene, free fatty acids,glycols and isopropanol (Loveland Industries, Inc.), unless otherwiseindicated. The formulated compounds were applied in 1 mL of liquidthrough a SUJ2 atomizer nozzle with 1/8 JJ custom body (Spraying SystemsCo.) positioned 1.27 cm (0.5 inches) above the top of each test unit.All experimental compounds in this screen were sprayed at 50 ppm andreplicated three times. After spraying of the formulated test compound,each test unit was allowed to dry for 1 hour and then a black, screenedcap was placed on top. The test units were held for 6 days in a growthchamber at 25° C. and 70% relative humidity. Plant feeding damage wasthen visually assessed.

Of the compounds tested, the following provided excellent levels ofplant protection (10% or less feeding damage): 5, 11, 18, 19, 24, 28,30, 32, 33, 34, 37, 38, 39, 40, 45, 45, 47, 48, 56, 57, 58, 59, 63, 64,75, 76, 77, 78, 79, 84, 85, 86, 87, 91, 93, 94, 95, 95, 97, 98, 99, 108,113, 114, 116, 115, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126,127, 128, 129, 130, 133, 135, 136, 141, 142, 143, 144, 145, 147, 148,149, 150, 151, 153, 154, 155, 156, 157, 158, 160, 161, 164, 165, 166,168, 159, 170, 174, 176, 177, 178, 179, 110, 181, 182, 183, 184, 185,186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199,200, 201, 202, 207, 208, 209, 210, 211, 212, 213, 214, 218, 219, 220,221, 222, 224, 229, 230, 231, 232, 233, 234, 236, 237, 238, 244, 246,247, 250, 257, 258, 259, 267, 268, 270, 271, 272, 273, 275, 276, 277,278, 279, 280, 281, 282, 283, 284, 287, 288, 289, 290, 291, 292, 293,294, 295, 297, 298, 299, 300, 301, 302, 305, 306, 307, 309, 313, 314,315, 316, 319, 320, 321, 322, 324, 325, 326, 327, 328, 329, 330, 335,336, 338, 339, 341, 344, 345, 346, 347, 348, 349, 351, 352, 356, 364,365, 366, 367, 370, 371, 372, 373, 374, 376, 377, 384, 387, 388, 390,391, 392, 393, 394, 395, 396, 401, 402, 404, 405, 406, 407, 409, 410,411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424,426, 428, 429, 430, 431, 432, 433, 434, 446, 449, 453, 454, 456, 457,458, 459, 460, 461, 462, 463, 468, 469, 470, 471, 472, 473, 474, 475,476, 477, 478, 479, 481, 482, 483, 484, 486, 487, 488, 489, 494, 497,499, 500, 501, 502, 505, 506, 512, 513, 514, 515, 516, 517, 518, 519,520, 521, 522, 523, 524, 526, 527, 528, 529, 530, 531, 532, 533, 534,535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548,549, 550, 351, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562,563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576,577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590,591, 592, 593, 594, 595, 596, 597, 598, 600, 601, 602, 603, 604, 605,606, 607, 608, 609, 611, 612, 613, 615, 616, 619, 620, 621, 622, 623,624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637,638, 639, 640, 641, 642, 643, 644, 645, 647, 648, 649, 650, 651, 655,656, 657, 658, 659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669,671, 672, 673, 674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684,685, 686, 687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698,699, 701, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 713, 714,715, 716, 717, 718, 719, 720, 721, 724, 725, 726, 727, 728, 729, 730,731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744,745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 756, 757, 759,762, 763, 766, 767, 768, 769, 771, 772, 773, 774, 775, 776, 777, 778,779, 780, 781, 782, 783, 784, 787, 790, 791, 792, 793, 794, 795, 796,797, 798, 801, 804, 809, 810, 811, 812, 813, 814, 815, 816, 817, 818,820, 321, 822, 823, 824, 825, 826, 829, 830, 831, 832 and 833.

Test B

For evaluating control of tobacco budworm (Heliothis virescens) the testunit consisted of a small open container with a 6-7 day old cotton plantinside. This was pre-infested with 8 2-day-old larvae on a piece ofinsect diet by use of a core sampler as described for Test A.

Test compounds were formulated and sprayed at 50 ppm as described forTest A. The applications were replicated three times. After spraying,the test units were maintained in a growth chamber and then visuallyrated as described for Test A.

Of the compounds tested, the following provided excellent levels ofplant protection (10% or less feeding damage): 8, 11, 18, 24, 28, 30,32, 33, 34, 37, 39, 46, 47, 48, 53, 56, 57, 58, 59, 60, 74, 75, 76, 77,78, 79, 80, 82, 84, 85, 86, 87, 88, 91, 93, 94, 95, 96, 113, 114, 115,116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 141, 142, 143,145, 147, 150, 151, 153, 154, 155, 156, 158, 160, 161, 164, 165, 166,168, 169, 170, 171, 174, 176, 177, 178, 179, 180, 181, 182, 183, 184,185, 186, 187, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199,200, 201, 202, 307, 208, 209, 210, 211, 212, 213, 214, 216, 218, 219,220, 221, 222, 223, 224, 229, 230, 231, 232, 233, 234, 236, 237, 238,239, 240, 244, 246, 247, 250, 257, 258, 267, 270, 271, 272, 273, 274,275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288,289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302,304, 305, 306, 307, 309, 313, 314, 315, 316, 319, 320, 321, 322, 324,325, 326, 327, 328, 336, 338, 339, 341, 345, 346, 348, 353, 356, 357,364, 366, 367, 370, 371, 372, 373, 374, 377, 381, 383, 384, 385, 387,388, 390, 391, 392, 393, 394, 395, 397, 399, 401, 402, 404, 405, 406,407, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421,422, 423, 424, 423, 429, 430, 431, 432, 433, 434, 444, 445, 446, 447,449, 453, 454, 456, 457, 458, 459, 460, 461, 462, 468, 469, 470, 471,472, 474, 473, 475, 476, 477, 478, 479, 481, 482, 483, 484, 486, 487,488, 489, 494, 497, 499, 500, 501, 502, 506, 511, 512, 513, 514, 515,516, 517, 518, 519, 520, 521, 522, 523, 524, 526, 527, 528, 529, 530,531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544,545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558,559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572,573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586,587, 588, 519, 590, 591, 592, 593, 594, 595, 596, 597, 598, 600, 601,602, 603, 605, 608, 609, 611, 612, 613, 614, 615, 616, 619, 620, 621,624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637,638, 639, 640, 641, 642, 643, 644, 645, 647, 648, 649, 650, 651, 655,656, 657, 658, 659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669,670, 671, 672, 673, 674, 675, 676, 677, 678, 679, 680, 681, 682, 683,684, 685, 686, 687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697,698, 699, 701, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 713,714, 715, 716, 717, 718, 719, 720, 721, 724, 725, 726, 727, 728, 729,730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 742, 743, 745,746, 747, 748, 749, 750, 751, 752, 753, 754 and 755.

Test C

For evaluating control of beet armyworm (Spodoptera exigua) the testunit consisted of a small open container with a 4-5-day-old corn (maize)plant inside. This was pre-infested with 10-15 1-day-old larvae on apiece of insect diet by use of a core sampler as described for Test A.

Test compounds were formulated and sprayed at 50 ppm as described forTest A. The applications were replicated three times. After spraying,the test traits were maintained in a growth chamber and then visuallyrated as described for Test A.

Of the compounds tested, the following provided excellent levels ofplant protection (10% or less feeding damage): 5, 8, 11, 13, 19, 24, 28,30, 32, 33, 34, 37, 38, 39, 46, 47, 48, 53, 56, 57, 58, 59, 60, 63, 64,74, 75, 76, 77, 78, 79, 84, 85, 86, 87, 88, 91, 92, 93, 94, 95, 96, 97,98, 99, 101, 102, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123,124, 125, 126, 127, 128, 129, 130, 133, 135, 136, 137, 141, 142, 143,144, 145, 146, 147, 148, 149, 150, 151, 153, 154, 155, 156, 157, 158,160, 161, 164, 165, 166, 168, 169, 170, 174, 176, 177, 178, 179, 180,182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 195, 196, 197,198, 199, 201, 202, 207, 208, 209, 210, 211, 212, 214, 218, 219, 221,224, 229, 230, 231, 232, 233, 234, 236, 237, 238, 239, 240, 244, 246,247, 250, 257, 258, 267, 270, 271, 272, 273, 274, 275, 276, 277, 278,279, 280, 281, 282, 283, 284, 286, 287, 288, 289, 290, 291, 292, 293,294, 295, 297, 298, 299, 300, 301, 302, 304, 305, 307, 309, 313, 314,315, 316, 319, 320, 321, 322, 324, 325, 326, 327, 328, 330, 336, 338,339, 341, 343, 344, 345, 346, 347, 348, 351, 352, 356, 364, 365, 366,367, 370, 371, 372, 373, 374, 376, 377, 380, 384, 385, 387, 388, 389,390, 391, 392, 393, 394, 395, 401, 402, 404, 405, 406, 407, 409, 410,413, 414, 418, 420, 422, 423, 424, 428, 429, 430, 431, 432, 433, 434,449, 453, 454, 456, 457, 458, 459, 460, 461, 462, 468, 469, 470, 471,472, 473, 474, 475, 476, 477, 478, 479, 481, 482, 483, 484, 486, 487,488, 494, 497, 499, 500, 501, 502, 506, 512, 513, 514, 515, 516, 517,518, 519, 520, 521, 522, 523, 524, 526, 527, 528, 529, 530, 531, 532,533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546,547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560,561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574,575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 516, 587, 588,589, 590, 591, 592, 593, 595, 596, 597, 598, 600, 601, 603, 605, 606,607, 608, 609, 611, 612, 613, 614, 616, 619, 620, 621, 624, 625, 626,627, 628, 629, 630, 531, 632, 633, 634, 635, 636, 637, 638, 639, 640,641, 642, 643, 644, 645, 647, 648, 650, 651, 655, 656, 657, 658, 659,660, 661, 662, 663, 664, 665, 666, 667, 669, 671, 672, 673, 674, 676,677, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688, 689, 690,691, 692, 693, 694, 695, 696, 697, 698, 699, 701, 702, 703, 704, 705,706, 707, 708, 709, 710, 711, 713, 714, 715, 719, 720, 721, 724, 725,726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739,740, 741, 742, 743, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754 and755.

Test D

For evaluating control of green peach aphid (Myzus persicae) throughcontact and/or systemic means, the test unit consisted of a small opencontainer with a 12-15-day-old radish plant inside. This waspre-infested by placing on a leaf of the test plant 30-40 insects on apiece of leaf excised from a culture plant (cut-leaf method). The larvaemoved onto the test plant as the leaf piece desiccated. Afterpre-infestation, the soil of the test unit was covered with a layer ofsand.

Test compounds were formulated using a solution containing 10% acetone,90% water and 300 ppm X-77® Spreader Lo-Foam Formula non-ionicsurfactant containing alkylarylpolyoxyethylene, free fatty acids,glycols and isopropanol (Loveland Industries, Inc.), unless otherwiseindicated. The formulated compounds were applied in 1 mL of liquidthrough a SUJ2 atomizer nozzle with 1/8 JJ custom body (Spraying SystemsCo.) positioned 1.27 cm (0.5 inches) above the top of each test unit.All experimental compounds in this screen were sprayed at 250 ppm andreplicated three times. After spraying of the formulated test compound,each test trait was allowed to dry for 1 hour and then a black, screenedcap was placed on top. The test units were held for 6 days in a growthchamber at 19-21° C. and 50-70% relative humidity. Each test unit wasthen visually assessed for insect mortality.

Of the compounds tested, the following resulted in at least 80%mortality: 283, 297, 370, 371, 372, 388, 431, 434, 469, 470, 472, 473,474, 476, 479, 486, 494, 497, 409, 500, 501, 502, 506, 512, 514, 515,516, 517, 518, 520, 530, 531, 532, 533, 534, 534, 537, 538, 539, 540,542, 543, 544, 546, 548, 549, 550, 551, 553, 554, 555, 557, 559, 560,561, 562, 503, 564, 565, 566, 567, 560, 571, 575, 576, 577, 578, 579,580, 582, 584, 590, 596, 507, 601, 602, 603, 604, 609, 611, 614, 619,620, 621, 624, 625, 626, 627, 629, 630, 631, 633, 638, 639, 640, 641,642, 643, 644, 645, 650, 651, 655, 656, 657, 661, 664, 669, 671, 672,673, 674, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 691, 698,699, 703, 708, 709, 710, 711, 719, 725, 726, 727, 728, 729, 730, 731,732, 733, 734, 735, 736, 737, 738, 739, 743, 744, 745, 746, 747, 743,749, 750, 751, 752, 753, 754, 771, 776, 779, 780, 781, 783, 784, 787,793, 809, 810, 811, 812, 821, 822, 823, 824, 825, 826, 830, 831, 832 and833.

Test E

For evaluating control of cotton melon aphid (Aphis gossypii) throughcontact and/or systemic means, the test unit consisted of a small opencontainer with a 6-7-day-old cotton plant inside. This was pre-infestedwith 30-40 insects on a piece of leaf according to the cut-leaf methoddescribed for Test D, and the soil of the test unit was covered with alayer of sand.

Test compounds were formulated and sprayed at 250 ppm as described forTest D. The applications were replicated three times. After spraying,the test units were maintained in a growth chamber and then visuallyrated as described for Test D.

Of the compounds tested, the following resulted in at least 80%mortality: 370, 371, 372, 348, 431, 470, 472, 474, 476, 486, 494, 497,500, 501, 506, 512, 514, 515, 516, 517, 518, 520, 530, 531, 532, 533,534, 536, 537, 338, 539, 540, 542, 543, 544, 546, 548, 549, 550, 551,553, 554, 555, 557, 559, 560, 561, 562, 563, 564, 566, 567, 568, 575,576, 577, 578, 579, 582, 596, 601, 602, 603, 604, 609, 611, 620, 621,624, 625, 626, 627, 628, 629, 630, 631, 638, 639, 640, 641, 642, 643,644, 655, 656, 657, 661, 672, 673, 679, 681, 686, 687, 691, 698, 699,703, 704, 706, 708, 709, 710, 711, 719, 725, 726, 727, 728, 729, 730,731, 732, 733, 734, 735, 736, 737, 738, 739, 743, 745, 746, 747, 748,749, 750, 751, 752, 753, 754, 755, 771, 774, 776, 777, 779, 780, 783,784, 787, 791, 793, 794, 809, 811, 812, 821, 822, 823, 825 and 826.

Test F

For evaluating control of corn planthopper (Peregrinus maidis) throughcontact and/or systemic means, the test unit consisted of a small opencontainer with a 3-4 day old corn (maize) plant (spike) inside. Whitesand was added to the top of the soil prior to application. Testcompounds were formulated and sprayed at 250 ppm and replicated threetimes as described for Test D. After spraying, the test units wereallowed to dry for 1 hour before they were post-infested with 10-20 cornplanthoppers (18 to 20 day old) nymphs) by sprinkling them onto the sandwith a salt shaker. A black, screened cap was placed on the top of thecylinder. The test unites were held for 6 days in a growth chamber at19-21° C. and 50-70% relative humidity. Each test unit was then visuallyassessed for insect mortality.

Of the compounds tested, the following resulted in at least 80%mortality: 370, 371, 372, 388, 431, 469, 470, 472, 474, 476, 486, 489,494, 497, 500, 501, 506, 512, 514, 515, 516, 517, 518, 520, 530, 531,532, 533, 534, 536, 537, 538, 539, 540, 542, 543, 544, 546, 548, 549,550, 551, 553, 554, 555, 557, 559, 560, 561, 562, 563, 564, 566, 567,568, 575, 576, 577, 578, 579, 582, 596, 601, 602, 603, 604, 609, 611,620, 621, 624, 625, 626, 627, 628, 629, 630, 631, 638, 639, 640, 641,642, 643, 644, 655, 656, 657, 661, 672, 673, 679, 681, 686, 687, 691,698, 699, 703, 704, 706, 708, 709, 710, 711, 719, 725, 726, 727, 728,729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 743, 745, 746,747, 748, 749, 750, 751, 752, 753, 754, 755, 771, 774, 776, 777, 779,780, 781, 783, 784, 787, 791, 793, 794, 809, 811, 812, 814, 821, 822,823, 825 and 826.

Test G

For evaluating control of potato leafhopper (Empoasca fabae Harris)through contact and/or systemic means, the test unit consisted of asmall open container with a 5-6 day old Longio bean plant (primaryleaves emerged) inside. White sand was added to the top of the soil andone of the primary leaves was excised prior to application. Testcompounds were formulated and sprayed at 250 ppm and replicated threetimes as described for Test D. After spraying, the test units wereallowed to dry for 1 hour before they were post-infested with 5 potatoleafhoppers (18 to 21 day old) adults). A black, screened cap is placedon the top of the cylinder. The test units were held for 6 days in agrowth chamber at 19-21° C. and 50-70% relative humidity. Each test unitwas then visually assessed for insect mortality.

Of the compounds tested, the following resulted in at least 80%mortality: 200, 233, 236, 283, 313, 316, 324, 370, 371, 372, 434, 456,457, 469, 470, 471, 472, 473, 474, 475, 476, 482, 486, 494, 497, 499,500, 501, 502, 506, 512, 514, 515, 516, 517, 518, 519, 520, 530, 531,533, 534, 536, 537, 538, 539, 542, 543, 544, 549, 550, 551, 553, 554,555, 557, 558, 559, 560, 561, 562, 563, 564, 566, 567, 568, 575, 576,577, 578, 579, 582, 584, 601, 603, 609, 611, 614, 619, 621, 625, 626,629, 630, 631, 632, 633, 634, 639, 640, 641, 643, 644, 655, 656, 657,662, 664, 672, 678, 679, 680, 681, 682, 683, 685, 686, 687, 703, 706,708, 710, 719, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736,737, 738, 742, 743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 753,754, 755, 766, 771, 776, 777, 779, 780, 781, 784, 787, 793, 794, 796,809, 810, 811, 812, 814, 821, 822, 824, 825, 826, 828, 831, 832 and 833.

Test H

For evaluating control of silverleaf whitefly (Bemisia tabaci), the testunit consisted of a 14-21-day-old cotton plant grown in Redi-earth®media (Scotts Co.) with at least two true leaves infested with 2nd and3rd instar nymphs on the underside of the leaves.

Test compounds were formulated in no more than 2 mL of acetone and thendiluted with water to 25-30 mL. The formulated compounds were appliedusing a flat fan air-assisted nozzle (Spraying Systems 122440) at 10 psi(69 kPa). Plants were sprayed to run-off on a turntable sprayer. Allexperimental compounds in this screen were sprayed at 250 ppm andreplicated three times. After spraying of the test compound, the testunits were held for 6 days in a growth chamber at 50-60% relativehumidity and 28° C. daytime and 24° C. nighttime temperature. Than theleaves were removed and the dead and live nymphs were counted tocalculate percent mortality.

Of the compounds tested, the following resulted in at least 80%mortality: 494, 497, 499, 500, 501, 502, 506, 512, 513, 514, 515, 516,517, 518, 520, 523, 530, 531, 532, 533, 534, 535, 536, 537, 538, 540,542, 543, 544, 549, 550, 551, 553, 554, 555, 557, 560, 575, 576, 577,578, 579, 601, 620, 625, 629, 641, 673, 686, 691 and 703.

Test I

For evaluating soil systemic control of tobacco budworm (Heliothisvirescens), cotton plants were grown in sassafras soil in 15-cm pots inaluminum mays. When the plants reached square stage (bud formation onthe plant) the plants were treated with the test compounds.

Test compounds were formulated in 0.25 mL of acetone and then dilutedwith water to provide solutions of 10 ppm. Ten mL of the treatmentsolutions was added to the pots weekly for four weeks, with fourreplicates of each treatment rate, One day after the second, third, andfourth treatments, 35-50 first instar Heliothis virescens larvae werebrushed on each plant with paintbrushes and placed on the terminal area,squares, and bolls. Five days after the last infestation with larvae theplants were rated for damage. Of the compounds tested, the followingprovided excellent levels of plant protection at 10 ppm (10% or lessfeeding damage) with excellent protection of squares and bolls includingno or minimal sepal damage: 214, 283 and 520.

Test J

Test H followed an alternative protocol for evaluating soil systemiccontrol of tobacco budworm (Heliothis virescens). Cotton plants weregrown in sassafras soil in 15-cm pots under greenhouse conditions. Whenthe plants reached square stage (bud formation on the plant) the soilsurface was treated with the test compounds.

Test compounds were formulated in 0.25 mL of acetone and then dilutedwith water. Ten mL of treatment solution containing 3 mg of compound wasadded to the soil surface of each pot. The plants were watered the nextday and each day following as needed. At 1, 2 and 4 days aftertreatment, leaves were excised for evaluation. Two sets of leaves wereselected from each plant: upper leaves at approximately second node fromterminal and with area greater than 25 cm² and lower leaves atapproximately third node from bottom and with area greater than 25 cm².The excised leaves were cut into 3 cm×2 cm sections and placed into testtrays made of high-impact styrene consisting of sixteen contiguouswells, each 6 cm wide, 4 cm long and 3 cm deep, with a clear plastic lidmolded so that it locked into each well by friction. Solidified agar wasplaced into the bottom of each well to maintain moisture for plantmaterial. One second instar tobacco budworm was placed into each wellwith plant material; wells were sealed and held at 25° C. and providedwith 16 hours of light per day.

Of the compounds tested, the following compounds provided excellentlevels of mortality (greater than 70% mortality) on upper leaves excisedat 4 days after treatment at the test rate; 497, 530 and 543.

Test K

For evaluating soil, systemic control of fall armyworm (Spodopterafrugiperda), corn (maize) plants (Pioneer #3394) were grown in smallpots for 5 days until they were at least 4 cm tall and the first leafwas unfurling.

Test compounds were dissolved in 0.25 mL of acetone and diluted withwater provide solutions of 1, 10, 50 and 200 ppm. One mL of the testsolution was applied by pipette to the surface of the soil in each pot,with eight plants for each compound/rate. The pots were covered and heldat 25° C. with 16 hours of light per day. The plants were watered thenext ay and each day following as needed. After 6 days, the plant matterabove the first leaf was excised and cut into 3-cm lengths. Each testunit was a high-impact styrene tray (Supplier: Clearpack Company, 11610Copenhagen Court, Franklin Park, Ill. 60131) consisting of sixteencontiguous wells each 6 cm wide, 4 cm long and 3 cm deep, with a clearplastic lid molded so that it locks into each well by friction.Solidified agar (2 to 4 mL) was placed onto the bottom of each well tomaintain moisture in the wells during the test. Each 3-cm length of cornplant matter was placed into a tray such that the plant matter wascontained within two wells. One second-instar fall armyworm (Spodopterafrugiperda) larva was placed in each well, the tray was covered and thenthe test units were held at 25° C. with 16 hours of light per day.Mortality was observed after four days.

LC₉₀ concentrations (test compound concentrations giving 90% kill of thelarvae) were calculated based on probit analysis (log linear regression)using a general linearized model (GLIM) of the SAS statistical computeranalysis product of SAS Institute (Cary, N.C., U.S.A.). Of the compoundstested, the following provided excellent levels of mortality, with LC₉₀values of 10 ppm or less: 200, 202, 313, 494, 497, 500, 513, 515, 516,518, 520, 531, 533, 535, 538, 542, 543 and 544.

Test L

For evaluating soil systemic control of Colorado potato beetle(Leptinotarsa decemlineata), transplanted tomato plants were grown in6-cm pots for 5 days until they were at the two true leaf stage.

Test compounds were dissolved in 0.25 mL of acetone and diluted withwater provide solutions of 5 ppm. Five mL of the appropriate testsolution was applied by pipette to the surface of the soil in each pot,followed by 5 mL of water, with eight plants for each compound rate. Thepots were covered and held at 25° C. with 16 hours of light per day. Theplants were watered the next day and each day following as needed. After4 days, one leaf from each plant was excised and placed into a well of atest tray as described in Test H. One 5-day old Colorado potato beetle(Leptinotarsa decemlineata) was placed in each well, the tray wascovered and then the test units were held at 25° C. with 16 hours oflight per day. Mortality was observed after four days.

Of the compounds tested, the following provided excellent levels ofmortality and feeding inhibition at 5 ppm: 214.

Test M

For evaluating control of boll weevil (Anthonomus g. grandis), samplesof the test compounds were dissolved in 1 mL of acetone. This solutionwas then diluted to 100 mL total volume using an aqueous 500 ppmsolution of Ortho X-77™ surfactant. Serial dilutions were made to obtain50 mL of 50 ppm concentration.

The diluted solutions of the test compounds were sprayed to run-off onthree-week-old cotton plants. The plants were placed on a rotatingturntable sprayer (10 rpm). Test solutions were applied using a flat fanair-assisted nozzle (Spraying Systems 122440) at 10 psi (60 kPa).Sprayed and dried plants were incased in a plastic cylinder. Twentyweevils were placed in each cylinder containing a whole cotton plant. Atthree days after infestation a feeding damage rating was taken.

Of the compounds tested, the following provided excellent levels ofplant protection at 50 ppm (10% or less feeding damage): 530 and 531.

Test N

For evaluating control of thrips (Frankliniella sp.) samples of the testcompounds were dissolved in 1 mL of acetone. This solution was thendiluted to 100 mL total volume using an aqueous 500 ppm solution ofOrtho X-77™ surfactant. Serial dilutions were made to obtain 50 mL of 10ppm concentration.

The diluted solutions of the test compounds were sprayed to run-off onthree-week-old cotton or soybean plants infested with thrips. The plantswere placed on a rotating turntable sprayer (10 rpm). Test solutionswere applied using a flat fan air-assisted nozzle (Spraying Systems122440) at 10 psi. (69 kPa). Sprayed and dried plants were incased in aplastic cylinder. At four days after application the total number ofdead thrips was recorded.

Of the compounds tested, the following resulted in at least 90%mortality at 10 ppm: 542.

Test O

Test O followed an alternative protocol for evaluating control ofColorado potato beetle (Leptinotarsa decemlineate). Several hours priorto spraying, 5 mg (100% active ingredient, ai) of the test compoundswere dissolved in 1 mL of acetone. Using the aqueous solution of 500 ppmof Ortho X-77™, the sample bottle was rinsed and added to the testcompounds. This sample solution was then brought to 100 mL with theaqueous solution. Serial dilutions are made to obtain 50 mL of 10 ppm.

Formulated experimental compounds were sprayed to run-off on three weekold potato or tomato plants. The plants were placed on a rotatingturntable sprayer (10 rpm). Test solutions were applied using a flat fanair-assisted nozzle (Spraying Systems 122440) at 10 psi (69 KPa). Oncethe plants were dried, leaves were excised from the treated plant. Theleaves were cut, and then the pieces were placed singly into a 5.5cm-by-3.5 cm cell of a sixteen-well plastic tray. Each cell contained a2.5 square of moistened chromatography paper to prevent desiccation. Onesecond instar larvae was placed in each cell. At three days afterinfestation total number of dead Colorado potato beetles was recorded.

Of the compounds tested, the following resulted in at least 90%mortality at 10 ppm: 497, 500, 530, 543, 544, 553, 562 and 684.

Test P

Seventy-eight cotton plants were grown in the greenhouse with naturallighting in Sassafras soil in six inch pots. When six true leaves wereon the plant (approximately 36 cm tall) the soil was drenched with asolution of Compound 497, 500, 530, 531 or 543. Each of the 5 compoundswas dissolved in 2 mL of acetone, and distilled water was added to make300 ppm solutions of each of the compounds. The pots were divided intosix groups (13 plants/treatment), and 10 mL of each solution was appliedover the soil surface of each group with one group left untreated. Theplants were arranged in the greenhouse in a randomized block design.Each treatment was divided into three groups for sampling at 24, 48, and96 hours.

Leaves were taken from the base and terminal of the plants. The leavesfrom the third node and the terminal leaves greater than 15 cm² weresampled per plant. One clipped leaf from each plant was cut into fourpieces and each piece was placed into an well with one second-instarlarvae of Heliothis virescens (tobacco budworm). Larval mortality (% M)was recorded 96 hours after sampling. The percentage of leaf feeding (%FF) was also recorded. Consumption of the leaf in the well was reportedas 0-100% (0 equals no feeding). Results are listed in Table P.

TABLE P Percent Larval Mortality and Feeding of Cotton Leaves Over Time24 h 48 h 96 h Compound Leaf position % M % FF % M % FF % M % FF 497terminal 29 50 65 50 81 10 base 13 80 46 100 59 20 500 terminal 4 60 3860 30 30 base 4 80 54 80 30 30 530 terminal 46 50 79 20 96 5 base 33 8063 50 70 5 531 terminal 25 40 42 40 55 10 base 13 60 33 80 29 10 543terminal 46 20 63 20 74 5 base 33 30 58 30 17 5 Untreated terminal 0 900 90 0 100 base 0 90 0 100 0 95

Test O

For evaluating german cockroach (Blatella germanica), Compound 531 wasmixed with water, and then blended into a slurry with equal, amounts (byweight) of peanut butter. The mixture was air dried leaving a peanutbutter bait with final concentration of the test substance as indicatedin the following table. Appropriately 1 gram of bait was placed intoeach test cage. Ten German cockroaches (Blatella germanica) were thenplaced into each cage, and provided water via a saturated cotton ball.The cages were held indoors, with indirect sunlight, and temperaturesranging from 22 to 31° C. Four test replicates were set up per rate.Evaluations were conducted 1, 2, 3, 5, and 7 days after treatment (DAT)by counting and removing the killed roaches found in each cage.

TABLE O German Cockroach Bait Test Average of Killed Cockroaches Rate 1DAT 2 DAT 3 DAT 5 DAT 7 DAT untreated 0.3 0.3 0.3 1 2  400 ppm 3.8 5.86.3 7 7  2000 ppm 6.3 8 8.8 9 9 10000 ppm 9.5 9.5 9.5 9.5 9.5

Test R

For evaluating control of fire ant (Solenopsis xyloni), Compound 531 wasmixed with water and then mixed into a slurry with equal amounts (byweight) of Niban granular bait with no active ingredient (supplied byNisus Corp.). The mixture was air dried, leaving a dry granular baitwith final concentration of the test substance as indicated in thefollowing table. The baits were uniformly sprinkled onto the sandsubstrate in each test cage. Fifty field-collected southern fire ants(Solenopsis xyloni) were then placed into each cage and provided watervia a saturated cotton ball. The cages were held indoors with indirectsunlight and temperatures ranging from 22 to 31° C. Four test replicateswere set up per rate. Evaluations were conducted at 1, 3, 7, 10, and 14days after treatment (DAT) by counting and removing the killed antsfound in each cage.

TABLE 6 Fire Ant Bait Test Average of Killed Fire Ants Rate 1 DAT 3 DAT7 DAT 10 DAT 14 DAT untreated 0.8 1.3 3.5 5.5 8.5   400 ppm 0.5 1.3 40.550 50  2,000 ppm 1 2 43 49.8 50 10,000 ppm 0 2.3 42.8 50 50

What is claimed is:
 1. A method for controlling lepidopteran,homopteran, hemipteran, thysanopteran and coleopteran insect pests,comprising: contacting the insects or their environment with anarthropodicidally effective amount of a compound of Formula I, anN-oxide or an agriculturally suitable salt thereof

wherein A and B are independently O or S; R¹ is H, C₁-C₆ alkyl, C₂-C₆alkoxycarbonyl or C₂-C₆ alkylcarbonyl; R² is H or C₁-C₆ alkyl; R³ is H;C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, or C₃-C₆ cycloalkyl, eachoptionally substituted with one or more substituents selected from thegroup consisting of halogen, CN, NO₂, hydroxy, C₁-C₄ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkoxy, C₁-C₄ alkylthio, C₁-C₄ alkylsulfinyl, C₁-C₄alkylsulfonyl, C₂-C₆ alkoxycarbonyl, C₂-C₆ alkylcarbonyl, C₃-C₆trialkylsilyl, phenyl, phenoxy, 5-membered heteroaromatic rings, and6-membered heteroaromatic rings; each phenyl, phenoxy, 5-memberedheteroaromatic ring, and 6-membered heteroaromatic ring optionallysubstituted with one to three substituents independently selected fromthe group consisting of C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₃-C₆cycloalkyl, C₁-C₄ haloalkyl, C₂-C₄ haloalkenyl, C₂-C₄ haloalkynyl, C₃-C₆halocycloalkyl, halogen, CN, NO₂, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₁-C₄alkylthio, C₁-C₄ alkylsulfinyl, C₁-C₄ alkylsulfonyl, C₁-C₄ alkylamino,C₂-C₈ dialkylamino, C₃-C₆ cycloalkylamino, C₄-C₈(alkyl)(cycloalkyl)amino, C₂-C₄ alkylcarbonyl, C₂-C₆ alkoxycarbonyl,C₂-C₆ alkylaminocarbonyl, C₃-C₈ dialkylaminocarbonyl and C₃-C₆trialkylsilyl; C₁-C₄ alkoxy; C₁-C₄ alkylamino; C₂-C₈ dialkylamino; C₃-C₆cycloalkylamino; C₂-C₆ alkoxycarbonyl or C₂-C₆ alkylcarbonyl; R⁴ is H,C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkyl, C₁-C₆haloalkyl, CN, halogen, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy or NO₂; R⁵ is H,C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₁-C₄ alkoxyalkyl, C₁-C₄ hydroxyalkyl,C(O)R¹⁰, CO₂R¹⁰, C(O)NR¹⁰R¹¹, halogen, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy,NR¹⁰R¹¹, N(R¹¹)C(O)R¹⁰, N(R¹¹)CO₂R¹⁰ or S(C)_(n)R¹²; R⁶ is H, C₁-C₆alkyl, C₁-C₆ haloalkyl, halogen, CN, C₁-C₄ alkoxy or C₁-C₄ haloalkoxy;R⁷ is C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkyl, C₁-C₆haloalkyl, C₂-C₆ haloalkenyl, C₂-C₆ haloalkynyl or C₃-C₆ halocycloalkyl;or R⁷ is a phenyl ring, a benzyl ring, a 5- or 6-membered heteroaromaticring, a naphthyl ring system or an aromatic 8-, 9- or 10-membered fusedheterobicyclic ring system, each ring or ring system optionallysubstituted with one to three substituents independently selected fromR⁹; R⁸ is H, C₁-C₆ alkyl, C₁-C₆ haloalkyl, halogen, C₁-C₄ alkoxy orC₁-C₄ haloalkoxy; each R⁹ is independently C₁-C₄ alkyl, C₂-C₄ alkenyl,C₂-C₄ alkynyl, C₃-C₆ cycloalkyl, C₁-C₄ haloalkyl, C₂-C₄ haloalkenyl,C₂-C₄ haloalkynyl, C₃-C₆ halocycloalkyl, halogen, CN, NO₂, C₁-C₄ alkoxy,C₁-C₄ haloalkoxy, C₁-C₄ alkylthio, C₁-C₄ alkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄ alkylamino, C₂-C₆ dialkylamino, C₃-C₆cycloalkylamino, C₄-C₈ (alkyl)(cycloalkyl)amino, C₂-C₄ alkylcarbonyl,C₂-C₆ alkoxycarbonyl, C₂-C₆ alkylaminocarbonyl, C₃-C₈dialkylaminocarbonyl or C₃-C₆ trialkylsilyl; R¹⁰ is H, C₁-C₄ alkyl orC₁-C₄ haloalkyl; R¹¹ is H or C₁-C₄ alkyl; R¹² is C₁-C₄ alkyl or C₁-C₄haloalkyl; and n is 0, 1 or 2; wherein the compound of Formula I isincluded in a composition further comprising an effective amount of atleast one additional biologically active compound or agent, and whereinat least one of the insect pests controlled is selected from the groupconsisting of Alabama argillacea Hübner (cotton leaf worm), Archipsargyrospila Walker (fruit tree leaf roller), A. rosana Linnaeus(European leaf roller) and other Archips species, Crambus caliginosellusClemens (corn root webworm), Crambus teterrellus Zincken (bluegrasswebworm), Cydia pomonella Linnaeus (codling moth), Earias insulanaBoisduval (spiny bollworm), Earias vittella Fabricius (spottedbollworm), Helicoverpa armigera Hübner (American bollworm), Helicoverpazea Boddie (corn earworm), Herpetogramma licarsisalis Walker (sodwebworm), Lobesia botrana Denis & Schiffermüller (grape berry moth),Pectinophora gossypiella Saunders (pink bollworm), Phyllocnistiscitrella Stainton (citrus leafminer), Pieris brassicae Linnaeus (largewhite butterfly), Pieris rapae Linnaeus (small white butterfly),Plutella xylostella Linnaeus (diamondback moth), Spodoptera exiguaHübner (beet armyworm), Spodoptera litura Fabricius (tobacco cutworm,cluster caterpillar), Trichoplusia ni Hübner (cabbage looper) and Tutaabsoluta Meyrick (tomato leafminer), Acyrthisiphon pisum Harris (peaaphid), Aphis craccivora Koch (cowpea aphid), Aphis pomi De Geer (appleaphid), Aphis spiraecola Patch (spirea aphid), Aulacorthum solaniKaltenbach (foxglove aphid), Chaetosiphon fragaefolii Cockerell(strawberry aphid), Dysaphis plantaginea Paaserini (rosy apple aphid),Eriosoma lanigerum Hausmann (woolly apple aphid), Hyalopterus pruniGeoffroy (mealy plum aphid), Lipaphis erysimi Kaltenbach (turnip aphid),Metopolophium dirrhodum Walker (cereal aphid), Macrosipum euphorbiaeThomas (potato aphid), Nasonovia ribisnigri Mosley (lettuce aphid),Pemphigus spp. (root aphids and gall aphids), Rhopalosiphum maidis Fitch(corn leaf aphid), Rhopalosiphum padi Linnaeus (bird cherry-oat aphid),Schizaphis graminum Rondani (greenbug), Therioaphis maculata Buckton(spotted alfalfa aphid), Toxoptera aurantii Boyer de Fonscolombe (blackcitrus aphid), and Toxoptera citricida Kirkaldy (brown citrus aphid);Adelges spp. (adelgids); Phylloxera devastatrix Pergande (pecanphylloxera); Bemisia argentifolii Bellows & Perring (silverleafwhitefly), Dialeurodes citri Ashmead (citrus whitefly) and Trialeurodesvaporariorum Westwood (greenhouse whitefly); Empoasca fabae Harris(potato leafhopper Nephotettix nigropictus Stål (rice leafhopper),Peregrinus maidis Ashmead (corn planthopper), Sogatodes orizicola Muir(rice delphacid), Typhlocyba pomaria McAtee white apple leafhopper,Erythroneoura spp. (grape leafhoppers); Magicidada septendecim Linnaeus(periodical cicada); Icerya purchasi Maskell (cottony cushion scale),Quadraspidiotus perniciosus Comstock (San Jose scale); Planococcus citriRisso (citrus mealybug); Pseudococcus spp. (other mealybug complex);Cacopsylla pyricola Foerster (pear psylla), Trioza diospyri Ashmead(persimmon psylla), Acrosternum hilare Say (green stink bug), Anasatristis De Geer (squash bug), Blissus leucopterus leucopterus Say(chinch bug), Corythuca gossypii Fabricius (cotton lace bug),Cyrtopeltis modesta Distant (tomato bug), Dysdercus suturellusHerrich-Schäffer (cotton stainer), Euchistus servus Say (brown stinkbug), Euchistus variolarius Palisot de Beauvois (one-spotted stink bug),Graptosthetus spp. (complex of seed bugs), Leptoglossus corculus Say(leaf-footed pine seed bug), Lygus lineolaris Palisot de Beauvois(tarnished plant bug), Oncopeltus fasciatus Dallas (large milkweed bug),Pseudatomoscelis seriatus Reuter (cotton fleahopper), Frankliniellaoccidentalis Pergande (western flower thrip), Scirthothrips citriMoulton (citrus thrip), Sericothrips variabilis Beach (soybean thrip),and Thrips tabaci Lindeman (onion thrip), Leptinotarsa decemlineata Say(Colorado potato beetle), Epilachna varivestis Mulsant (Mexican beanbeetle) and wireworms of the genera Agriotes, Athous or Limonius). 2.The method of claim 1 wherein A and B are both O; R⁷ is a phenyl ring ora 5- or 6-membered heteroaromatic ring selected from the groupconsisting of

each ring optionally substituted with one to three substituentsindependently selected from R⁹; Q is O, S, NH or NR⁹; and W, X, Y and Zare independently N, CH or CR⁹, provided that in J-3 and J-4 at leastone of W, X, Y or Z is N.
 3. The method of claim 2 wherein R¹, R² and R⁸are all H; R³ is C₁-C₄ alkyl optionally substituted with halogen, CN,OCH₃ or S(O)_(p)CH₃; R⁴ group is attached at position 2; R⁴ is CH₃, CF₃,OCF₃, OCHF₂, CN or halogen; R⁵ is H, CH₃ or halogen; R⁶ is CH₃, CF₃ orhalogen; R⁷ is phenyl or 2-pyridinyl, each optionally substituted; and pis 0, 1 or
 2. 4. The method of claim 3 wherein R³ is C₁-C₄ alkyl and R⁶is CF₃.
 5. The method of claim 3 wherein R³ is C₁-C₄ alkyl and R⁶ is Clor Br.
 6. The method of claim 1 wherein the at least one additionalbiologically active compound or agent is selected from arthropodicidesof the group consisting of pyrethroids, carbamates, neonicotinoids,neuronal sodium channel blockers, insecticidal macrocyclic lactones,γ-aminobutyric acid (GABA) antagonists, insecticidal ureas and juvenilehormone mimics.
 7. The method of claim 1 wherein the at least oneadditional biologically active compound or agent is selected from thegroup consisting of abamectin, acephate, acetamiprid, amidoflumet(S-1955), avermectin, azadirachtin, azinphos-methyl, bifenthrin,binfenazate, buprofezin, carbofuran, chlorfenapyr, chlorfluazuron,chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clothianidin,cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda-cyhalothrin,cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon,diflubenzuron, dimethoate, diofenolan, emamectin, endosulfan,esfenvalerate, ethiprole, fenothicarb, fenoxycarb, fenpropathrin,fenproximate, fenvalerate, fipronil, flonicamid, flucythrinate,tau-fluvalinate, flufenerim (UR-50701), flufenoxuron, fonophos,halofenozide, hexaflumuron, imidacloprid, indoxacarb, isofenphos,lufenuron, malathion, metaldehyde, methamidophos, methidathion,methomyl, methoprene, methoxychlor, monocrotophos, methoxyfenozide,nithiazin, novaluron, noviflumuron (XDE-007), oxamyl, parathion,parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon,pirimicarb, profenofos, pymetrozine, pyridalyl, pyriproxyfen, rotenone,spinosad, spiromesifin (BSN 2060), sulprofos, tebufenozide,teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, thiacloprid,thiamethoxam, thiodicarb, thiosultap-sodium, tralomethrin, trichlorfonand triflumuron, aldicarb, oxamyl, fenamiphos, amitraz, chinomethionat,chlorobenzilate, cyhexatin, dicofol, dienochlor, etoxazole, fenazaquin,fenbutatin oxide, fenpropathrin, fenpyroximate, hexythiazox, propargite,pyridaben, tebufenpyrad; and biological agents such as Bacillusthuringiensis including ssp. aizawai and kurstaki, Bacillusthuringiensis delta endotoxin, baculovirus, and entomopathogenicbacteria, virus and fungi.
 8. The method of claim 1 wherein the at leastone additional biologically active compound or agent is selected fromthe group consisting of cypermethrin, cyhalothrin, cyfluthrin andbeta-cyfluthrin, esfenvalerate, fenvalerate, tralomethrin, fenothicarb,methomyl, oxamyl, thiodicarb, clothianidin, imidacloprid, thiacloprid,indoxacarb, spinosad, abamectin, avermectin, emamectin, endosulfan,ethiprole, fipronil, flufenoxuron, triflumuron, diofenolan,pyriproxyfen, pymetrozine, amitraz, Bacillus thuringiensis, Bacillusthuringiensis delta endotoxin and entomophagous fungi.
 9. The method ofclaim 1 wherein a plant is contacted by the composition applied as asoil drench of a liquid formulation.
 10. The method of claim 1 whereinthe pest is selected from the group consisting of beet armyworm(Spodoptera exigua Hübner) and cabbage looper (Trichoplusia ni Hübner).11. The method of claim 1 wherein the pest is selected from the groupconsisting of corn root webworm (Crambus caliginosellus Clemens) and sodwebworm (Herpetogramma licarsisalis Walker.
 12. The method of claim 1wherein the pest is selected from the group consisting of codling moth(Cydia pomonella Linnaeus) and grape berry moth (Endopiza viteanaClemens).
 13. The method of claim 1 wherein the pest is selected fromthe group consisting of diamondback moth (Plutella xylostella Linnaeus)and pink bollworm (Pectinophora gossypiella Saunders).
 14. The method ofclaim 1 wherein the pest is a Colorado potato beetle (Leptinotarsadecemlineata Say).
 15. The method of claim 1 wherein the pest is anonion thrip (Thrips tabaci Lindeman).